Project description:Gene expression profiling was carried out on peripheral blood mononuclear cell mRNA samples collected from 53 female breast cancer patients at 6- or 12-month follow-ups in a randomized controlled trial of Cognitive Behavioral Stress Management or an active control condition. The primary research question is whether gene expression differs in patients treated with Cogntive Behavioral Stress Management vs control conditions. Gene expression profiling was carried out on peripheral blood mononuclear cell mRNA samples collected from 53 female breast cancer patients at 6- or 12-month follow-ups in a randomized controlled trial of Cognitive Behavioral Stress Management or an active control condition. The primary research question is whether gene expression differs in patients treated with Cogntive Behavioral Stress Management vs control conditions. Risk prediction
Project description:Gene expression profiling was carried out on peripheral blood mononuclear cell mRNA samples collected from 53 female breast cancer patients at 6- or 12-month follow-ups in a randomized controlled trial of Cognitive Behavioral Stress Management or an active control condition. The primary research question is whether gene expression differs in patients treated with Cogntive Behavioral Stress Management vs control conditions.
Project description:To investigate the differential expression of miRNAs in circulating leukocytes of patients with MMD. The results showed 12 differentially expressed miRNAs in leukocytes of MMD patients compared with controls (fold change > 2.0 and P < 0.05), of which 7 were up-regulated and 5 were down-regulated.
Project description:Chronic stress is associated with anxiety and cognitive impairment. Repeated social defeat (RSD) in mice induces anxiety-like behavior driven by microglia and the recruitment of inflammatory monocytes to the brain. Nonetheless, it is unclear how microglia communicate with other cells to modulate the physiological and behavioral responses to stress. Using single-cell (sc)RNAseq, novel stress-associated microglia were identified in the hippocampus and defined by RNA profiles of cytokine/chemokine signaling, cellular stress, and phagocytosis. Microglia depletion with a CSF1R antagonist (PLX5622) attenuated the stress-associated profile of leukocytes, endothelia, and astrocytes. Furthermore, RSD-induced social withdrawal and cognitive impairment were microglia dependent, but social avoidance was microglia independent. Furthermore, single-nuclei (sn)RNAseq showed robust responses to RSD in hippocampal neurons that were both microglia dependent and independent. Notably, stress-induced CREB, oxytocin, and glutamatergic signaling in neurons were microglia dependent. Collectively, these stress-associated microglia influenced transcriptional profiles in the hippocampus linked to social and cognitive deficits.
Project description:Differential diagnosis of adrenocortical adenoma and carcinoma is of pivotal clinical relevance, as the prognosis and clinical management of benign and malignant adrenocortical tumours is entirely different. Circulating microRNAs are promising biomarker candidates of malignancy in several tumours. In the present study we investigate circulating microRNAs in adrenocortical tumours and to evaluate their potential applicability as biomarkers of malignancy. For the miRNA profiling, 8 preoperative plasma samples obtained from patients with adrenocortical adenomas and carcinomas and were studied by microarray.
Project description:Circulating tumor cells in the peripheral have proven to be independent prognostic factors for overall survival the monitoring of therapeutic success of human breast cancer patients. Postmortem morphologic evidence also points towards the presence of circulating tumor cells in the peripheral blood of dogs with metastatic canine mammary tumors. However, the existence of these cells has not been verified in canines in vivo and they have not been isolated and characterized due to the lack of appropriate and canine specific detection methods. In the present study a panel of 73 genes with high expression levels in canine mammary carcinoma cells and but not in peripheral blood leukocytes were identified using microarray analysis. From this panel, six mRNA markers, AGR2, ATP8B1, CRYAB, F3 and IRX3, were expressed in canine mammary carcinoma cells but not in the peripheral blood of dogs. All six RT-PCR assays, were sensitive enough detect one carcinoma cell admixed in 106 or more peripheral blood leukocytes, a common concentration of circulating tumor cells in the peripheral blood of human breast cancer patients. These five mRNA markers may therefore be used to detect canine mammary circulating tumor cells and to study their spatio-temporal presence in the peripheral blood of canine patients.
Project description:Circulating tumor cells in the peripheral have proven to be independent prognostic factors for overall survival the monitoring of therapeutic success of human breast cancer patients. Postmortem morphologic evidence also points towards the presence of circulating tumor cells in the peripheral blood of dogs with metastatic canine mammary tumors. However, the existence of these cells has not been verified in canines in vivo and they have not been isolated and characterized due to the lack of appropriate and canine specific detection methods. In the present study a panel of 73 genes with high expression levels in canine mammary carcinoma cells and but not in peripheral blood leukocytes were identified using microarray analysis. From this panel, six mRNA markers, AGR2, ATP8B1, CRYAB, F3 and IRX3, were expressed in canine mammary carcinoma cells but not in the peripheral blood of dogs. All six RT-PCR assays, were sensitive enough detect one carcinoma cell admixed in 106 or more peripheral blood leukocytes, a common concentration of circulating tumor cells in the peripheral blood of human breast cancer patients. These five mRNA markers may therefore be used to detect canine mammary circulating tumor cells and to study their spatio-temporal presence in the peripheral blood of canine patients. Two canine mammary carcinoma cell lines, CMM115 and CMM26, and peripheral blood samples of 3 healthy dog donors were used for microarray analysis. All blood donors were female, showed no signs of infectious or inflammatory disease and did not have mammary gland tumors or any other identifiable tumors at the time of collection. Furthermore, blood cell count and blood chemistry were unremarkable in all dogs.
Project description:Circulating tumour cells in women with advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER+/HER2- primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2. Cultured circulating tumour cells maintain discrete HER2+ and HER2- subpopulations: HER2+ circulating tumour cells are more proliferative but not addicted to HER2, consistent with activation of multiple signalling pathways; HER2- circulating tumour cells show activation of Notch and DNA damage pathways, exhibiting resistance to cytotoxic chemotherapy, but sensitivity to Notch inhibition. HER2+ and HER2- circulating tumour cells interconvert spontaneously, with cells of one phenotype producing daughters of the opposite within four cell doublings. Although HER2+ and HER2- circulating tumour cells have comparable tumour initiating potential, differential proliferation favours the HER2+ state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2- phenotype. Simultaneous treatment with paclitaxel and Notch inhibitors achieves sustained suppression of tumorigenesis in orthotopic circulating tumour cell-derived tumour models. Together, these results point to distinct yet interconverting phenotypes within patient-derived circulating tumour cells, contributing to progression of breast cancer and acquisition of drug resistance. Seventy-four single candidate CTCs from two representative ER+/HER2- patients (BRx-42 and BRx-82) and 14 triple negative patients were isolated via micromanipulation and subjected to single-cell RNA-sequencing. Thirteen candidate CTCs expressed PTPRC at a level higher than 10 reads-per-million, so were deemed potential White Blood Cells and therefore dropped from further consideration. Expression profiles of CTCs expressing ERBB2 at a level greater than 10 RPM were compared with those expressing ERBB2 at a level less than 10 RPM.
Project description:Objective was to examine acute gene expression responses to physiologic oral glucose ingestion in human circulating leukocytes. Microarray study of human circulating leukocytes sampled before, 1 hour after and 2 hours after glucose ingestion was performed. The present study demonstrated 36 genes which showed acute gene expression change in human leukocytes within 1 hour after glucose ingestion and suggest that leukocytes participate in the inflammatory process induced by acute hyperglycemia. Microarray study of human circulating leukocytes sampled before, 1 hour after and 2 hours after glucose ingestion