Stress is a powerful modulator of neuroendocrine, behavioral, and immunological functions. So far, the molecular mechanisms of response to stressors still remain elusive. In the current study, after 10 days of repeated chronic stress (hot-dry environment and electric foot-shock), a murine model of combinedstress (CS) was created in the SPF Wistar rats. Meanwhile, we established an ulcerative-colitis (UC) rat model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol enema according to previous studies. The blood, hypothalamus, and colon tissues of these rats from CS, normal control (NC), UC and sham (SH) groups, were collected for further investigations. Comparing to the NC group, the serum levels of T3, T4, fT3 and fT4 were obviously decreased in the CS group after chronic stress, indicating that thyroid dysfunction was induced by long-term combined stress. Moreover, the application of RNAseq and subsequent analyses revealed that neurological disorder and immunosuppression were also caused in the hypothalamus and colon tissues, respectively. Comparing with SH group, besides the induced colon infammation, thyroid dysfuntion and neurological disorder were also produced in the UC group, suggesting that hypothalamic-pituitary-thyroid (HPT) axis and gastrointestinal system might not function in isolation, but rather, have intricate crosstalks. Overall design: Thyroid dysfuntion was induced by combined stress
Thyroid Dysfunction, Neurological Disorder and Immunosuppression as the Consequences of Long-term Combined Stress.
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View SamplesWe report the transcriptional changes in Drosophila after administration of Actin or buffer control Overall design: Examination of transcriptional responses to actin versus buffer injected flies at 3,6 and 24 hours post injection (each time point includes triplicate samples)
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in <i>Drosophila melanogaster</i>.
Sex, Specimen part, Cell line, Subject
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PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sex, Age, Specimen part, Cell line
View SamplesThe PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sex, Age, Specimen part
View SamplesThe PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sex, Specimen part
View SamplesThe PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Specimen part, Cell line
View SamplesIn our efforts to evaluate the function of the IL-8 receptor CXCR2 in Acute Lymphoblastic Leukemia (ALL) cells, we made use of SB225002 (N-(2-hydroxy-4-nitrophenyl)-N-(2-bromophenyl)urea), a drug initially described as a CXCR2 antagonist. Although the CXCR2 receptor was found to be non-functional in ALL, B- and T-ALL cell lines were sensitive to SB225002.
SB225002 Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia Cells through the Activation of GLIPR1.
Specimen part, Cell line
View SamplesMost studies have analysed the effects of high dose radiation such as atomic bomb survivors in Japan, people exposed during the Chernobyl nuclear accident, patients undergoing radiation therapy, uranium miners, etc. However, it has been difficult to measure and assess the risk of cancer in people exposed to lower doses of ionising radiation, such as the people living at high altitudes, who are exposed to more natural background radiation from cosmic rays than people at sea level. We measured the genomic response to X-ray ionising radiation (10 cGy and 100 cGy) in a skin tissue model to compare the effects of low and high dose ionising radiation at different time points. The microarray data was then analysed using state-of-the art upside-down pyramid computational systems biology methods to identify genes contributing to the difference in the response to the different radiation doses.
Comparison of low and high dose ionising radiation using topological analysis of gene coexpression networks.
Time
View SamplesUnderstanding how developmental and environmental signals are integrated to produce specific responses is one of the main challenges of modern biology. Hormones and, most importantly, interactions between different hormones serve as crucial regulators of plant growth and development, playing central roles in the coordination of internal developmental processes with the environment. Herein, a combination of physiological, genetic, cellular, and whole-genome expression profiling approaches has been employed to investigate the mechanisms of interaction between two key plant hormones, ethylene and auxin.
Multilevel interactions between ethylene and auxin in Arabidopsis roots.
No sample metadata fields
View SamplesHyperthermia (HT) treatments in combination with either chemotherapy, radiotherapy or both are used for patients with cancer in various organs. However, the acquisition of thermotolerance in cancer cells due to the increase in cytoprotective proteins attenuates the therapeutic effects of HT. BAG3 (BCL2-associated athanogene 3) is a cytoprotective protein that acts against various stresses including heat stress. Recently, we demonstrated that the inhibition of BAG3 improves cell death sensitivity to HT in cancer cells. However, a detailed molecular mechanism involved in the enhancement of HT sensitivity by BAG3-knockdown (KD) in cancer cells is unclear.
Network analysis of genes involved in the enhancement of hyperthermia sensitivity by the knockdown of BAG3 in human oral squamous cell carcinoma cells.
Sex, Age, Specimen part, Cell line
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