Mouse cells cyclophosphamide treated vs untreated
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Federica Moschella
PROVIDER: E-GEOD-27440 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Unraveling cancer chemoimmunotherapy mechanisms by gene and protein expression profiling of responses to cyclophosphamide.
Moschella Federica F Valentini Mara M Aricò Eleonora E Macchia Iole I Sestili Paola P D'Urso Maria Teresa MT Alessandri Cristiano C Belardelli Filippo F Proietti Enrico E
Cancer research 20110328 10
Certain chemotherapeutic drugs, such as cyclophosphamide (CTX), 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 currently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we methodically profiled the effects of CTX on gene expression in bone marrow, spleen, and peripheral blood, a ...[more]
Similar Datasets
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: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: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:RNA-seq analysis was performed using RNA isolated from three tumor models (GL261 glioma, LLC Lewis lung carcinoma, B16F10 melanoma) implanted subcutaneousy in C57BL/6 mice, or in ICR scid mice. Mice were untreated or were treated with cyclophosphamide (CPA) given on a 6-day repeating metronomic schedule (CPA/6d), except as noted. Results from these global transcriptome analysis indicated substantial elevation of basal GL261 immune infiltration and strong activation by CPA/6d treatment of GL261 immune stimulatory pathways and their upstream regulators, but without preferential depletion of negative immune regulators compared to LLC and B16F10 tumors. In LLC tumors, where CPA/6d treatment was found to be anti-angiogenic, CPA/6d suppressed VEGFA target genes and down regulated cell adhesion and leukocyte transendothelial migration genes. In GL261 tumors implanted in adaptive immune-deficient scid mice, where CPA/6d-induced GL261 regression is incomplete and late tumor growth rebound can occur, T cell receptor signaling and certain cytokine-cytokine receptor responses seen in B6 mice were deficient. Extending the CPA treatment interval from 6 to 9 days (CPA/9d) â which results in a strong but transient natural killer cell response followed by early tumor growth rebound â induced fewer cytokines and increased expression of drug metabolism genes. Taken together, these findings elucidate molecular response pathways activated by intermittent metronomic CPA treatment and identify deficiencies that characterize immune-unresponsive tumor models and drug schedules. RNA isolated from various tumor cell lines implanted s.c in C57BL/6 mice or scid mice, untreated or treated with cyclophosphamide (CPA) given on a metronomic schedule, were prepared and used for stranded or unstranded RNA-seq.
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Project description:Cyclophosphamide (CPA) treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. However, little is known about the underlying mechanisms of innate immune cell mobilization and recruitment, or about the role of DNA damage and cell stress response pathways in eliciting the anti-tumor immune responses linked to tumor regression. To address these questions, we compared untreated and 6-day metronomic cyclophosphamide-treated human U251 glioblastoma xenografts by human microarray analysis to identify responsive tumor cell-specific factors. Human glioma U251 tumors were implanted sc in scid immunodeficient mice then treated with cyclophosphamide at 140 mg/kg every 6 days. Tumors were collected 6 days after the second cyclophosphamide treatment and also 6 days after the third cyclophosphamide treatment. Tumor RNA was then analyzed on two color Agilent human expression microarrays comparing cyclophosphamide-treated RNA to untreated control tumor RNA.
2015-05-04 | E-GEOD-60867 | biostudies-arrayexpress
Project description:Cyclophosphamide (CPA) treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. However, little is known about the underlying mechanisms of innate immune cell mobilization and recruitment, or about the role of DNA damage and cell stress response pathways in eliciting the anti-tumor immune responses linked to tumor regression. To address these questions, we compared untreated and 6-day metronomic cyclophosphamide-treated human U251 glioblastoma xenografts by mouse microarray analysis to identify responsive mouse (host) cell-specific factors. Human glioma U251 tumors were implanted sc in scid immunodeficient mice then treated with cyclophosphamide at 140 mg/kg every 6 days. Tumors were collected 6 days after the second cyclophosphamide treatment and also 6 days after the third cyclophosphamide treatment. Tumor RNA was then analyzed on two color Agilent mouse expression microarrays comparing cyclophosphamide-treated RNA to untreated control tumor RNA.
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Project description:Cyclophosphamide (CPA) treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. However, little is known about the underlying mechanisms of innate immune cell mobilization and recruitment, or about the role of DNA damage and cell stress response pathways in eliciting the anti-tumor immune responses linked to tumor regression. To address these questions, we compared untreated and 6-day metronomic cyclophosphamide-treated rat 9L gliosarcoma xenografts by mouse microarray analysis to identify responsive mouse (host) cell-specific factors. Rat glioma 9L tumors were implanted sc in scid immunodeficient mice then treated with cyclophosphamide at 140 mg/kg every 6 days. Tumors were collected 6 days after the fourth cyclophosphamide treatment. Tumor RNA was then analyzed on two color Agilent mouse expression microarrays comparing cyclophosphamide-treated RNA to untreated control tumor RNA.
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