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Project description:Impact of a pre-operative exercise intervention on breast cancer proliferation and gene expression
| PRJNA531611 | ENA
Project description:There is growing evidence that uncontrolled activation of the PI3K/Akt/mTOR pathway contributes to the development and progression of breast cancer. Inhibition of this pathway has antitumour effects in preclinical studies and efficacy in combination with other agents in breast cancer patients. The aim of this study is to characterise the effects of pre-operative everolimus treatment in primary breast cancer patients and to identify potential molecular predictors of response. Twenty-seven patients with oestrogen receptor (ER)-positive breast cancer completed 11–14 days of neoadjuvant treatment with 5-mg everolimus. Core biopsies were taken before and after treatment and analysed using Illumina HumanRef-8 v2 Expression BeadChips. Changes in proliferation (Ki67) and phospho-AKT were measured on diagnostic core biopsies/resection samples embedded in paraffin by immunohistochemistry to determine response to treatment. Patients that responded to everolimus treatment with significant reductions in proliferation (fall in % Ki67 positive cells) also had significant decreases in the expression of genes involved in cell cycle (P = 8.70E−09) and p53 signalling (P = 0.01) pathways. Highly proliferating tumours that have a poor prognosis exhibited dramatic reductions in the expression of cell cycle genes following everolimus treatment. The genes that most clearly separated responding from non-responding pre-treatment tumours were those involved with protein modification and dephosphorylation, including DYNLRB2, ERBB4, PTPN13, ULK2 and DUSP16. The majority of ER-positive breast tumours treated with everolimus showed a significant reduction in genes involved with proliferation, these may serve as markers of response and predict which patients will derive most benefit from mTOR inhibition.
2018-08-30 | GSE119262 | GEO
Project description:To assess the impact of pre-operative breast MRI on surgical waiting time, and to identify factors contributing to the delay.A retrospective cohort study involving 1274 patients was conducted after obtaining institutional ethics review. Surgical candidates for newly diagnosed breast cancer from 2007 to 2013 at a tertiary center were divided into 2 groups: those who had pre-operative MRI and those who did not. Linear regression using matched populations was used to compare the surgical waiting times, defined as time from the date of the first positive biopsy to the date of surgery. Potential influences on surgical waiting time and subgroup analysis were obtained using median regression analysis and the Kruskal-Wallis test.Mean surgical waiting time was 57.9 days (95% CI: 55.6-60.1) for MRI patients, compared to 46.8 days (95% CI: 45.1-48.9) for the control group, after matching for potential confounding factors (p<0.0001). Increased surgical waiting time was associated with more favorable pathology, later year of diagnosis, older patient age, surgeon and summer time. Second-look ultrasound and subsequent biopsies were associated with increased waiting time (p = 0.001).Pre-operative breast MRI increased surgical waiting time by 11 days using a conventional average of differences, and by 12 days after using a full matching statistical method (p<0.0001), with the main contributor being additional post-MRI procedures and imaging.
| S-EPMC5221790 | biostudies-literature
Project description:Purpose: This study aimed to investigate the effects of a pre-hip arthroscopy exercise intervention on hip strength, pain, and function in individuals with femoroacetabular impingement (FAI). Methods: A total of 20 individuals with FAI completed a 10-week, partially supervised exercise programme; this included three phases of increasing resistance and functionality, consisting of four to six exercises per phase. Hip strength in all six directions; hip pain; function, as measured by the Hip disability and Osteoarthritis Outcome Score (HOOS); and objective physical function, as measured by the Timed Stair Climb test, were determined before and after the intervention. Results: Maximum isometric hip strength significantly increased in abduction (p=0.008), adduction (p=0.021), and internal rotation (p=0.006) at follow-up. Increases in flexion, extension, and external rotation strength did not reach statistical significance. Self-reported HOOS pain (p<0.01) and activities of daily living sub-scale scores (p<0.01) significantly improved at follow-up. Timed Stair Climb times (p<0.001) also significantly decreased at follow-up. Conclusion: A 10-week exercise programme can be safely completed by adults with FAI before surgery, and statistically significant changes in strength, function, and self-reported clinical outcomes can be achieved.
| S-EPMC5963554 | biostudies-literature
Project description:BackgroundDespite the recent development of technologies giving detailed images of tumours in vivo, direct or indirect ways to measure how many cells are actually killed by a treatment or are resistant to it are still beyond our reach.MethodsWe designed a simple model of tumour progression during treatment, based on descriptions of the key phenomena of proliferation, quiescence, cell killing and resistance, and giving as output the macroscopically measurable tumour volume and growth fraction. The model was applied to a database of the time course of volumes of breast cancer in patients undergoing pre-operative chemotherapy, for which the initial estimate of proliferating cells by the measure of the percentage of Ki67-positive cells was available.ResultsThe analysis recognises different patterns of response to treatment. In one subgroup of patients the fitting implied drug resistance. In another subgroup there was a shift to higher sensitivity during the therapy. In the subgroup of patients where killing of cycling cells had the highest score, the drugs showed variable efficacy against quiescent cells.ConclusionThe approach was feasible, providing items of information not otherwise available. Additional data, particularly sequential Ki67 measures, could be added to the system, potentially reducing uncertainty in estimates of parameter values.
| S-EPMC2496916 | biostudies-literature
Project description:Neoadjuvant treated patients were selected from the Genomstudy of the University Women`s Clinic Heidelberg (2009-2016). This study includes primary breast cancer cases that were newly diagnosed at the University women's clinic of Heidelberg and had given their informed consent for participating in this study. This study was approved by the Ethical Committee of the Medical Faculty in Heidelberg. All cases were female and Caucasian. Fresh core needle biopsies and fresh tumor tissue were examined by a pathologist, snap-frozen in liquid nitrogen and stored at -80C within 15 min after sampling. Total RNA as well as DNA and protein were extracted by applying the QIAGEN All Prep Kit. All eluates were stored at -80C until usage. A sample swap most probably occurred for patient 207, so 207-S is actually in the T condition and 207-T in the S condition.
2017-05-15 | E-MTAB-4632 | biostudies-arrayexpress
Project description:BackgroundPrehabilitation is thought to reduce post-operative respiratory complications by optimising fitness before surgery. This prospective, single-centre study aimed to establish the effect of pre-operative exercise on cardiorespiratory fitness in oesophageal cancer patients and characterise the effect of adherence and weekly physical activity on response to prehabilitation.MethodsPatients received a personalised, home-based pre-operative exercise programme and self-reported their adherence each week. Cardiorespiratory fitness (pVO2max and O2 pulse) was assessed at diagnosis, following completion of neoadjuvant chemotherapy (NAC) and immediately before surgery. Study outcomes included changes in fitness and post-operative pneumonia.ResultsSixty-seven patients with oesophageal cancer underwent prehabilitation followed by surgery between January 2016 and December 2018. Fitness was preserved during NAC and then increased prior to surgery (pV02max Δ = +2.6 ml min-1, 95% CI 1.2-4.0 p = 0.001; O2 pulse Δ = +1.4 ml beat-1 95% CI 0.5-2.3 p = 0.001). Patients with higher baseline fitness completed more physical activity. Regression analyses found adherence was associated with improvement in fitness immediately before surgery (p = 0.048), and the amount of physical activity completed was associated with the risk of post-operative pneumonia (p = 0.035).ConclusionPre-operative exercise can maintain cardiorespiratory fitness during NAC and facilitate an increase in fitness before surgery. Greater exercise volumes were associated with a lower risk of post-operative pneumonia, highlighting the importance progressing exercise programmes throughout prehabilitation. Patients with high baseline fitness completed more physical activity and may require less supervision to reach their exercise goals. Further research is needed to explore stratified approaches to prehabilitation.
| S-EPMC8007503 | biostudies-literature
Project description:The purpose of this study is to see whether exercise can improve the health and well-being of patients scheduled to undergo surgery for a bowel related condition.
| 2221084 | ecrin-mdr-crc
Project description:Gene expression profiling of pre-operative mTOR inhibitor everolimus treatment in breast cancer
| PRJNA488625 | ENA