Pericyte induced reprogramming of the bone marrow microenvironment drives stem and cancer cell quiescence
Ontology highlight
ABSTRACT: This dataset was generated by RNA sequencing of whole tibiae of C57Bl/6 mice. For young mice; tibiae from 6-weeks-old mice were used and for aged mice tibiae from 70-weeks-old mice were used. The control, radiation, and chemotherapy samples were generated using 14-weeks-old mice. For radiation treatment; mice were exposed to sublethal irradiation while for chemotherapy samples mice were treated with carboplatin and tibiae were collected
Project description:Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity. Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 Gy or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA. Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation and cholesterol metabolism. We found significantly enhanced expression of pro-inflammatory cytokines (TNF-, TGF-, IL-1 and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low density lipoprotein (LDL) and oxidized LDL was increased whereas that of high density lipoprotein was decreased by irradiation. Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy.
Project description:Non Small Cell Lung Cancer (NSCLC) causes the premature death of over 1 million people worldwide each year, but remains inadequately understood at the molecular level. To provide new insights for NSCLC treatment we performed a molecular characterisation of wild type and platinum drugs resistance in A549 cells. Transcriptome profiling revealed contrasting patterns of gene expression in sensitive and resistant cells and identified genes whose expression was highly correlated with the platinum drugs. Our results revealed a gene set of 15 transcripts whose expression was highly correlated with platinum-resistance in NSCLC A549 cell lines.
Project description:Oral mucositis (OM) is a common, painful and often treatment-limiting side effect of radiotherapy (RT) for head and neck cancer (HNC) patients. Unstimulated saliva was collected before the first radiotherapy application in 50 HNC patients. 41 out of 50 patients developed OM (grade III) during radiotherapy, of which 14 patients even displayed an early OM (grade III) at low radiation dose of 30 Gy. Nine patients did not develop OM (grade III). Using an LC-MS/MS approach 5,323 tryptic peptides were assigned to 487 distinct proteins (≥2 peptides) in the data set. The levels of 48 proteins differed significantly (p<0.05) between patients developing OM or not. 17 proteins displayed increased levels (≥1.3-fold) and 31 proteins decreased in level in OM, respectively. Furthermore, using partial least square analysis proteins patterns could be used to distinguish subjects which did not develop grade III OM even after 70 Gy total dose (n=9) and those displaying early OM (grade III at <30 Gy total dose, n=14). Using leave one out cross validation 37 of 41 patients (90%) developing OM could be correctly assigned indicating that prognostic proteome signatures may help to identify patients that should be specifically monitored to increase overall effectiveness of RT treatment.
Project description:We have previously shown that during lactation, osteocytes directly remodel their perilacunar and pericanalicular matrix, thereby mobilizing calcium and contributing to maternal bone loss. To identify genes potentially responsible for perilacunar remodeling, microarray analysis was performed on osteocytes from CD-1 virgin and lactating mice and mice sacrificed on day 7 post weaning. By comparing how gene expression changes in osteocytes among virgin, lactation and post lactation, the goal is to identify the genes osteocytes use to remodel their perilacunar matrix To identify genes responsible for perilacunar remodeling, microarray analysis was performed on tibiae from CD-1 virgin and lactating mice and mice sacrificed on day 7 post weaning. Periosteum and bone marrow were removed from the tibiae and the bone fragments underwent sequential collagenase/trypsin digestion and were examined histologically to ensure removal of all surface cells and confirm osteocyte enrichment prior to RNA extraction. Microarray Affy M430 arrays, n=3 per group were performed and Genepattern and Bioconductor were used to analyse the microdata.
Project description:The patient-derived xenograft (PDX) model retains the heterogeneity of patient tumors, allowing a means to not only examine efficacy of a therapy across a population, but also study crucial aspects of cancer biology in response to treatment. Herein we describe the development and characterization of an ovarian-PDX model in order to study the development of chemoresistance. We demonstrate that PDX tumors are not simply composed of tumor-initiating cells, but recapitulate the original tumor’s heterogeneity, oncogene expression profiles, and clinical response to chemotherapy. Combined carboplatin/paclitaxel treatment of PDX tumors enriches the cancer stem cell populations, but persistent tumors are not entirely composed of these populations. RNA-Seq analysis of treated PDX tumors compared to untreated tumors demonstrates a consistently contrasting genetic profile after therapy, suggesting similar, but few, pathways are mediating chemoresistance. The pathways most significantly altered included Protein Kinase A signaling, GNRH signaling, and sphingosine-1-phosphate signaling. Pathways and genes identified by this methodology represent novel approaches to targeting the chemoresistant population in ovarian cancer 6 pairs of Patient-Derived Xenografts (PDX) were ananlyzed using RNA-seq for a total of 12 samples. Each pair consists of a treated and untreated PDX of ovarian cancer. Treated Ovarian cancer PDXs were treated with 4 weeks of a combination of carboplatin and taxol. RNA was isolated and converted to cDNA. RNA-seq was conductred on the Illumina HiSeq 2000 with 50 bp paired end sequencing
Project description:Profiling of proteolytic events mouse kidneys during cisplatin-induced kidney damage. Kidneys from vehicle-treated mice are compared to cisplatin-treated mice and cisplatin treatment in animals preconditioned by hypoxia or calory restriction regimes.
Project description:NF-E2-related factor 2 (Nrf2), a transcription factor activated by oxidative stress, induces phase II conjugating or antioxidant enzymes. In the present study, we examined the effect of Nrf2 knockout (Nrf2 KO) on the kidney injury induced by cisplatin using cDNA microarray analyses. A transcriptomic approach enabled us to extract gene clusters which show significantly different mRNA expression patterns between wild type (WT) and Nrf2 KO mice. In the experimental set, WT vehicle (WT-Veh) and WT cisplatin (WT-Cis) groups were included in our previous GEO database (GSE35257) because the two groups were simultaneously shared with Nrf2 KO vehicle (Nrf2 KO-Veh) and Nrf2 KO cisplatin (Nrf2 KO-Cis) groups in the current report. Copyright (c) 2012 by Korea Food & Drug Administration. WT and Nrf2 KO C57BL/6 mice (9 weeks old, male) were intraperitoneally injected with vehicle (saline) or a single dose of cisplatin (15 mg/kg body weight). The cDNA microarray experiments were done for the kidney of mice 3 days after treatment. Three animals were used per group. WT-Veh and WT-Cis groups were already deposited in GSE35257.
Project description:Methods currently available to estimate the post-mortem submerged interval (PMSI) of cadavers in water suffer from poor accuracy, being mostly based on morphological examination of the remains. Proteins present within bones have recently attracted more attention from researchers interested in the estimation of the post-mortem interval (PMI) in terrestrial environments. Despite the great potential of proteomic methods for PMI estimation, their application to aquatic environments has not yet been explored. In this study, we examined whether four different types of aquatic environment (tap water, saltwater, pond water and chlorinated water) affected the proteome of mice bones with increasing PMSIs (from zero to three weeks).
Project description:The phosphorylomics data of liver tissue of 16-week-old HFHC-induced mice treated with saline or breviscapine for 8 weeks. The mice fed with high fat and high cholesterol were also divided into two groups. The control group was treated with normal saline for 8W, and the drug group was treated with breviscapine for 8W n=3.
Project description:Chemotherapy resistance adversely impacts the treatment of some individuals with esophageal cancer. Identifying chemotherapy resistance might help tailor clinical treatments. In this study the impact of microRNAs on chemotherapy resistance in esophageal cancer was investigated. We used microarrays to detail the global programme of microRNA expression underlying chemotherapy resistance and identified distinct classes of up-regulated microRNAs in generated chemotherapy resistant cell lines. An in-vitro model of acquired chemotherapy resistance in esophageal adeno- (EAC) and squamous cell carcinoma (SCC) cells was used, and microRNA expression profiles for cisplatin or 5-fluorouracil (FU) resistant variants vs. chemotherapy sensitive controls were compared using microarray. These results were further validated using qRT-PCR techniques (not shown in this submission).