Alterations in the gene expression profile in patients treated with cyclophosphamide
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE51907 | GEO | 2013/11/15
SECONDARY ACCESSION(S): PRJNA225805
REPOSITORIES: GEO
Similar Datasets
Project description:Investigation of whole genome gene expression level changes in patients treated with cyclophosphamide We have studied the gene expression profile for 11 patients with different types of hematological malignancies but all of them have been treated with CP i.v. Eleven patients were enrolled in this study. All of them were treated by i.v. infusion of CP 60 mg/kg/day once for 2 days followed by TBI. Blood samples were collected from each patient before the start of CP infusion, 6 h after CP first dose, before CP second dose (24 h after first dose) and 6 h after it.
2013-11-15 | E-GEOD-51907 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE27421: Mouse bone marrow cyclophosphamide treated vs untreated GSE27422: Mouse peripheral blood leukocytes cyclophosphamide treated vs untreated GSE27423: Mouse spleen cyclophosphamide treated vs untreated Refer to individual Series
2011-04-27 | E-GEOD-27440 | biostudies-arrayexpress
Project description:Analysis the effect of cyclophosphamide on splenocytes gene expression. Certain chemotherapeutic drugs such as cyclophosphamide can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is presently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we methodically profiled the effects of cyclophosphamide on gene expression in bone marrow, spleen and peripheral blood, and on cytokine expression in plasma and bone marrow of tumor-bearing mice. Gene and protein expression were modulated early and transiently by cyclophosphamide, leading to upregulation of a variety of immunomodulatory factors, including danger signals, pattern recognition receptors, inflammatory mediators, growth factors, cytokines, chemokines and chemokine receptors. These factors are involved in sensing cyclophosphamide myelotoxicity and activating repair mechanisms, which, in turn, stimulate immunoactivation events that promote efficacy. In particular, cyclophosphamide induced a T helper 17 (Th17)-related gene signature associated with an increase in Th17, Th1 and activated CD25+CD4+Foxp3- T lymphocytes and a slight recovery of regulatory T-cells. By analyzing gene and protein expression kinetics and their relationship to the antitumor efficacy of different therapeutic schedules of combination, we determined that optimal timing for performing adoptive immunotherapy is approximately 1 day after cyclophosphamide treatment. Together, our findings highlight factors that may propel the efficacy of chemoimmunotherapy, offering a mechanistic glimpse of the important immune modulatory effects of cyclophosphamide Four-condition experiment, Untreated mice - Cyclophosphamide-treated mice 1 day - Cyclophosphamide-treated mice 2 days - Cyclophosphamide-treated mice 5 days. Biological replicates: 5, controls: 5, independently harvested. Two replicates per array.
2011-04-27 | E-GEOD-27423 | biostudies-arrayexpress
Project description:To identify N6-methyladenosine RNA methylome in cyclophosphamide-treated neonatal rat cardiac myocytes (NRCMs), MeRIP-seq of NRCMs treated with cyclophosphamide (CYP) or solvent control (DMSO) were performed.
2021-09-23 | GSE184294 | GEO
Project description:Certain anticancer drugs, particularly cyclophosphamide (CTX), were shown to enhance the antitumor efficacy of immunotherapy through different immunomodulatory mechanisms. A better understanding of the cellular and molecular basis of CTX-mediated immunomodulation is needed to improve the efficacy of chemoimmunotherapy. Transcript profiling and flow cytometry were used to explore CTX immune-enhancing activity in patients with hematologic malignancies. A single high-dose treatment quickly (1-2 days) induced an extensive transcriptional modulation in peripheral blood mononuclear cells, leading to the reduction of cell cycle and biosynthetic/metabolic processes and to the augmentation of transcripts related to DNA damage and cell death (p53 signaling pathway, CDKN1A, CCND3, BAX, BBC3, BID, DDB2, SESN2), of scavenger receptors involved in the recognition of death (MARCO, CD68, CD163L1, SCARB2), of antigen processing/presentation mediators (CIITA, CTSC, CTSL1, CTSZ, GLA, GAA, TPP1, NEU1, SLC11A1, LAMP-2), of T cell activation markers (CD69, OX40) and, noticeably, of a type I interferon (IFN-I) signature (OAS1, CXCL10, BAFF, IFITM2, IFI6, IRF5, IRF7, STAT2, UBE2L6, UNC93B1, ISG20L1, TYK2). Moreover, the plasma levels of IFN-I-induced proinflammatory mediators (CXCL10, CCL2, IL-8, BAFF) were increased by treatment. Accordingly, CTX preconditioning induced both monocyte and lymphocyte activation, leading to the expansion of CD14+CD16+ monocytes, of HLA-DR+, IL8RA+, MARCO+ monocytes/dendritic cells and of CD69+, OX40+, IL8RA+ lymphocytes. Altogether, these data define for the first time the immunomodulatory factors induced by CTX in humans and indicate that preconditioning chemotherapy may stimulate immunity as a consequence of danger perception associated to its cytotoxic action on blood cells, through p53 and IFN-I-related mechanisms. Four-condition experiment, Untreated (10 Biological replicates) - Cyclophosphamide-treated 1 day (10 Biological replicates) - Cyclophosphamide-treated 2 days (8 Biological replicates) - Cyclophosphamide-treated 5 days (5 Biological replicates). Each sample labeled with Cy5 and co-hybridized with Cy3-labeled M-bM-^@M-^\referenceM-bM-^@M-^] aRNA. One replicate per array.
2013-09-02 | E-GEOD-39324 | biostudies-arrayexpress
Project description:Acquired imatinib resistance in chronic myelogenous leukemia (CML) can be the consequence of mutations in the kinase domain of BCR-ABL or increased protein levels. However, as in other malignancies, acquired resistance to cytostatic drugs is a common reason for treatment failure or disease progression. As a model for drug resistance, we developed a CML cell line resistant to cyclophosphamide (CP). Using oligonucleotide arrays, we examined changes in global gene expression. Selected genes were also examined by real-time PCR and flow cytometry. Neither the parent nor the resistant lines had mutations in their ATP binding domain. Filtering genes with a low-base line expression, a total of 239 genes showed significant changes (162 up- and 77 down-regulated) in the resistant clone. Most of the up-regulated genes were associated with metabolism, signal transduction, or encoded enzymes. The gene for aldehyde dehydrogenase 1 was over-expressed more than 2000 fold in the resistant clone. BCR-ABL was expressed in both cell lines to a comparable extent. When exposed to the tyrosine kinase inhibitors imatinib and nilotinib, both lines were sensitive. In conclusion, we found multiple genetic changes in a CML cell line resistant to CP related to metabolism, signal transduction or apoptosis. Despite these changes, the resistant cells retained sensitivity to tyrosine kinase inhibitors. Experiment Overall Design: A CML cell line and a CP resistant subline were compared by gene array. In addition other markers, the expression of BCR-ABL and the sensitivity to tyrosine kinase inhibitors were tested.
2009-04-25 | E-GEOD-7114 | biostudies-arrayexpress
Project description:Analysis the effect of cyclophosphamide on bone marrow gene expression. Certain chemotherapeutic drugs such as cyclophosphamide can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is presently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we methodically profiled the effects of cyclophosphamide on gene expression in bone marrow, spleen and peripheral blood, and on cytokine expression in plasma and bone marrow of tumor-bearing mice. Gene and protein expression were modulated early and transiently by cyclophosphamide, leading to upregulation of a variety of immunomodulatory factors, including danger signals, pattern recognition receptors, inflammatory mediators, growth factors, cytokines, chemokines and chemokine receptors. These factors are involved in sensing cyclophosphamide myelotoxicity and activating repair mechanisms, which, in turn, stimulate immunoactivation events that promote efficacy. In particular, cyclophosphamide induced a T helper 17 (Th17)-related gene signature associated with an increase in Th17, Th1 and activated CD25+CD4+Foxp3- T lymphocytes and a slight recovery of regulatory T-cells. By analyzing gene and protein expression kinetics and their relationship to the antitumor efficacy of different therapeutic schedules of combination, we determined that optimal timing for performing adoptive immunotherapy is approximately 1 day after cyclophosphamide treatment. Together, our findings highlight factors that may propel the efficacy of chemoimmunotherapy, offering a mechanistic glimpse of the important immune modulatory effects of cyclophosphamide Four-condition experiment, Untreated mice - Cyclophosphamide-treated mice 1 day - Cyclophosphamide-treated mice 2 days - Cyclophosphamide-treated mice 5 days. Biological replicates: 5, controls: 5, independently harvested. Two replicates per array.
2011-04-27 | E-GEOD-27421 | biostudies-arrayexpress
Project description:Analysis of the effect of cyclophosphamide on peripheral blood leukocyte gene expression. Certain chemotherapeutic drugs such as cyclophosphamide can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is presently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we methodically profiled the effects of cyclophosphamide on gene expression in bone marrow, spleen and peripheral blood, and on cytokine expression in plasma and bone marrow of tumor-bearing mice. Gene and protein expression were modulated early and transiently by cyclophosphamide, leading to upregulation of a variety of immunomodulatory factors, including danger signals, pattern recognition receptors, inflammatory mediators, growth factors, cytokines, chemokines and chemokine receptors. These factors are involved in sensing cyclophosphamide myelotoxicity and activating repair mechanisms, which, in turn, stimulate immunoactivation events that promote efficacy. In particular, cyclophosphamide induced a T helper 17 (Th17)-related gene signature associated with an increase in Th17, Th1 and activated CD25+CD4+Foxp3- T lymphocytes and a slight recovery of regulatory T-cells. By analyzing gene and protein expression kinetics and their relationship to the antitumor efficacy of different therapeutic schedules of combination, we determined that optimal timing for performing adoptive immunotherapy is approximately 1 day after cyclophosphamide treatment. Together, our findings highlight factors that may propel the efficacy of chemoimmunotherapy, offering a mechanistic glimpse of the important immune modulatory effects of cyclophosphamide Four-condition experiment, Untreated mice - Cyclophosphamide-treated mice 1 day - Cyclophosphamide-treated mice 2 days - Cyclophosphamide-treated mice 5 days. Biological replicates: 4, controls: 4, independently harvested. Two replicates per array.
2011-04-27 | E-GEOD-27422 | biostudies-arrayexpress
Project description:BDC2.5/NOD mice were treated with cyclophosphamide to induce type 1 diabetes. Their pancreatic islets were analyzed before treatment (Day 0) and as treatment progressed (Days 1 through 3) Keywords = type I diabetes Keywords = cyclophosphamide Keywords = BDC2.5 Keywords = NOD Keywords = pancreas Keywords = islets Keywords: time-course
2005-02-09 | GSE2254 | GEO
Project description:Acquired imatinib resistance in chronic myelogenous leukemia (CML) can be the consequence of mutations in the kinase domain of BCR-ABL or increased protein levels. However, as in other malignancies, acquired resistance to cytostatic drugs is a common reason for treatment failure or disease progression. As a model for drug resistance, we developed a CML cell line resistant to cyclophosphamide (CP). Using oligonucleotide arrays, we examined changes in global gene expression. Selected genes were also examined by real-time PCR and flow cytometry. Neither the parent nor the resistant lines had mutations in their ATP binding domain. Filtering genes with a low-base line expression, a total of 239 genes showed significant changes (162 up- and 77 down-regulated) in the resistant clone. Most of the up-regulated genes were associated with metabolism, signal transduction, or encoded enzymes. The gene for aldehyde dehydrogenase 1 was over-expressed more than 2000 fold in the resistant clone. BCR-ABL was expressed in both cell lines to a comparable extent. When exposed to the tyrosine kinase inhibitors imatinib and nilotinib, both lines were sensitive. In conclusion, we found multiple genetic changes in a CML cell line resistant to CP related to metabolism, signal transduction or apoptosis. Despite these changes, the resistant cells retained sensitivity to tyrosine kinase inhibitors. Keywords: Cell type comparison
2007-02-24 | GSE7114 | GEO