Predictors of depression in breast cancer patients during and after radiotherapy: Role of chemotherapy and the inflammatory response
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ABSTRACT: Chemotherapy and the inflammatory response were associated with persistent depressive symptoms in breast cancer patients undergoing radiation. Treatments targeting inflammation before radiation may reduce depression post radiation therapy, especially in patients who have been treated previously with chemotherapy. Total RNA was isolated from the peripheral blood mononuclear cells (PBMC) obtained from the women (n=61) with Stage 0-III breast cancer treated with or without chemotherapy.
Project description:Chemotherapy and the inflammatory response were associated with persistent depressive symptoms in breast cancer patients undergoing radiation. Treatments targeting inflammation before radiation may reduce depression post radiation therapy, especially in patients who have been treated previously with chemotherapy.
Project description:<p>The goal of this study was to identify SNPs and CNPs that are associated with development of normal tissue toxicities resulting from radiotherapy for prostate cancer. The study population includes approximately 1,400 men treated with brachytherapy, external beam radiation therapy, or a combination of the two treatments, and assessed for adverse effects at baseline and following radiotherapy. Three toxicity endpoints were investigated using a two-stage GWAS approach: urinary morbidity, rectal bleeding and erectile dysfunction. The study sample was split into a discovery set (N=367) and a replication set (N=417), and an additional 647 samples, which were not part of this original cohort, were also included as an independent replication set. The replication set was developed via collaboration developed under the framework of the Radiogenomics Consortium (RGC).</p> <p>The long-term goal of this project, and other radiogenomics projects lead by the RGC, is two-fold: 1) Develop an assay capable of predicting which cancer patients are most likely to develop radiation injuries resulting from treatment with a standard RT protocol, and 2) Obtain information to assist with the elucidation of the molecular pathways responsible for radiation-induced normal tissue toxicities. These studies focus on multiple cancer types including prostate, breast, lung, and head and neck cancers.</p>
Project description:Purpose:The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. We hypothesized that due to similarities between radiation and chemotherapy induced cellular response mechanisms, radiation responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Materials and Methods: Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human breast cancer subtypes were irradiated to identify radiation responsive genes. These murine radiation induced genes were then converted to their human orthologs. These genes were then used to develop a predictor of pathologic complete response (pCR) that was validated on two independent published neoadjuvant chemotherapy data sets of genomic data with response. Results: A radiation induced gene signature consisting of 30 genes was identified on a training set of 337 human primary breast cancer tumor samples that was prognostic for survival. Mean expression of this signature was calculated for individual samples in two independent published datasets and was found to be significantly predictive of pathologic complete response. Multivariate logistic regression analysis in both independent datasets showed that this 30 gene signature added significant predictive information independent of that provided by standard clinical predictors and other gene expression based predictors of pathologic complete response. Conclusion: This study provides new biologic information regarding response to neoadjuvant chemotherapy and a means of possibly improving the prediction of pathologic complete response. reference x sample
Project description:In this study, we evaluated the association between protein content in serum exosomes and severity of CIPN. Women with early stage breast cancer receiving adjuvant taxane chemotherapy were assessed with the FACT-Ntx score and serum was collected before and after the taxane treatment.
Project description:The depressive-like behavior in animals is usually assessed by standardized behavioral tests such as the forced swimming test. However, the findings of these tests may be affected by individual variability among animals, which may hinder the discovery of genes responsible for depression. Few reports have showed the influence of individual variability in identifying the genes associated with depressive-like behavior. In this study, we measured the immobility ratio (% immobility in 5 min) in the forced swimming test in 106 male Wistar rats. According to the distribution of individual immobility ratio, the rats were divided into three groups: the control group with immobility ratio -1 to +1 standard deviation (SD) from the mean, the depressive group with immobility ratio +1 to +2 SD above the mean, and the anti-depressive group with immobility ratio -1 to -2 SD below the mean. Microarray analysis was used to identify the genes differentially expressed by depressive group rats in the prefrontal cortex and cerebellum. The differentially expressed genes in both brain regions of the depressive group were Alas2, Gh1, Hba-a2, Hbb, Hbb-b1, Hbe2, LOC689064, Mrps10, Mybpc, Olf6415, and Pfkb1. Ingenuity pathway analysis identified Gh1 as a hub gene in the networks of the differentially expressed genes in both brain regions. This study indicates that inherent differences in depressive-like behavior may be related to the Gh1 expression in the cerebellum and prefrontal cortex. We measured the immobility ratio of 106 normal rats using the forced swimming test and statistically analysis. We selected the rats exhibitting depressive-like behavior or average in the 106 rats. Total RNA was prepareted from the cerebellum and prefrontal cortex. An equal amount of RNA from 4 rats in each group was pooled and used for microarray analysis.
Project description:A transcriptome signature which discriminate efficiently primary and radiation induced breast angiosarcomas can be generated from FFPE tumor samples.FFPE samples are good material to unlock relevant informations from tumors. The transcriptome of 35 FFPE breast angiosarcomas (10 primary and 25 radiation induced) were analysed using Affymetrix Human Exon 1.0 ST arrays according to the FFPE dedicated protocole from NuGEN and compared to paired fresh frozen samples previously analysed. FF Samples are also available in Array Express as E-MEXP-3252.
Project description:A primary human cell line, UACC-SARC1, was derived from a resection for a neoadjuvant chemotherapy resistant radiation induced spindle cell sarcoma. The sarcoma cell line was derived from a breast cancer patient who was treated with breast conserving surgery and radiation therapy. This radiation induced sarcoma is a malignant fibrous histiocytoma. Comparative genomic hybridization was performed on the source material and on the established cell line 20 of the cell line
Project description:Purpose:The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. We hypothesized that due to similarities between radiation and chemotherapy induced cellular response mechanisms, radiation responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Materials and Methods: Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human breast cancer subtypes were irradiated to identify radiation responsive genes. These murine radiation induced genes were then converted to their human orthologs. These genes were then used to develop a predictor of pathologic complete response (pCR) that was validated on two independent published neoadjuvant chemotherapy data sets of genomic data with response. Results: A radiation induced gene signature consisting of 30 genes was identified on a training set of 337 human primary breast cancer tumor samples that was prognostic for survival. Mean expression of this signature was calculated for individual samples in two independent published datasets and was found to be significantly predictive of pathologic complete response. Multivariate logistic regression analysis in both independent datasets showed that this 30 gene signature added significant predictive information independent of that provided by standard clinical predictors and other gene expression based predictors of pathologic complete response. Conclusion: This study provides new biologic information regarding response to neoadjuvant chemotherapy and a means of possibly improving the prediction of pathologic complete response.
Project description:Radiation therapy (RT) is one of the most commonly used anti-cancer therapies. However, the landscape of cellular response to irradiation, especially to a single high-dose irradiation, remains largely unknown. In this study, we performed a whole-genome CRISPR loss-of-function screen and revealed temporal inherent and acquired responses to RT. Specifically, we found that loss of the IL1R1 pathway led to cellular resistance to RT. This is in part due to the involvement of radiation-induced IL1R1-dependent transcriptional regulation, which relies on the NF-κB pathway. Moreover, the mitochondrial anti-apoptotic pathway, particularly the BCL2L1 gene, is crucially important for cell survival following radiation. BCL2L1 inhibition combined with RT dramatically impeded tumor growth in several breast cancer cell lines and syngeneic models. Taken together, our results suggest that the combination of an apoptosis inhibitor such as a BCL2L1 inhibitor with RT may represent a promising anti-cancer strategy for solid cancers including breast cancer.