Safety evaluation of a short-term infusion of ramucirumab for GI tract cancer patients
Ontology highlight
ABSTRACT:
DISEASE(S): Gastric And Colorectal Cancer
PROVIDER: 2644505 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:The RANGE study (NCT02426125) evaluated ramucirumab (an anti-VEGFR2 monoclonal antibody) in patients with platinum-refractory advanced urothelial carcinoma (UC). Here, we use programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) and transcriptome analysis to evaluate the association of immune and angiogenesis pathways, and molecular subtypes, with overall survival (OS) in UC. Higher PD-L1 IHC and immune pathway scores, but not angiogenesis scores, are associated with greater ramucirumab OS benefit. Additionally, Basal subtypes, which have higher PD-L1 IHC and immune/angiogenesis pathway scores, show greater ramucirumab OS benefit compared to Luminal subtypes, which have relatively lower scores. Multivariable analysis suggest patients from East Asia as having lower immune/angiogenesis signature scores, which correlates with decreased ramucirumab OS benefit. Our data highlight the utility of multiple biomarkers including PD-L1, molecular subtype, and immune phenotype in identifying patients with UC who might derive the greatest benefit from treatment with ramucirumab. Please note that the RANGE clinical trial data generated in this study have been deposited at www.vivli.org. RANGE clinical trial data are available under restricted access to protect patient privacy, and access can be obtained by submitting a request. For details on submitting a request, see the instructions provided at www.vivli.org. For specific study details, see here: https://search.vivli.org/?search=NCT02426125.
2022-03-14 | GSE198269 | GEO
Project description:Study of the short term (within the first 330 seconds) transcriptional response of S.cerevisiae upon a sudden addition of glucose. Keywords: glucose pulse, chemostat culture, glucose catabolite repression
2005-12-16 | GSE3821 | GEO
Project description:Gastric Cancer (GC) is one of the most serious cancers with high incidence and mortality all over the world. Chemotherapy hadn’t led to desirable effect and targeted therapy brings about a new stage to cancer treatment. Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. It is well known that gold nanorod, a nontoxic biocompatible nanomaterial, is an especially promising candidate for cancer theranostic. In this study, Ramucirumab (Ab) were first modified by gold nanoparticles to enhance uptake efficiency. The simple Nano-delivery system had taken perfect aggregation effect in vivo even better than 5-fold Ab treatment. Gold nanomaterials, especially gold nanorod (AuNR), could induce direct cytotoxic effect to cancer cell in the presence of Ab, while Ab or gold nanoparticle themselves couldn’t lead to such direct killing effect even at an extremely high concentration. Transcriptomic and proteomic analyses revealed the mechanism of this direct cytotoxicity.
2021-08-06 | GSE181369 | GEO
Project description:Short-term intensive fasting rejuvenates erythropoiesis
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Project description:OBJECTIVE: To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR). BACKGROUND: Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we show how short-term CR protects the mouse heart from ischemia. METHODS: Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food over a period of 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. Prior to MI (d8), the left ventricles (LV) of AL and CR mice were collected for Western blot, DNA and microRNA (miR) analyses. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI. RESULTS: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). cDNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM). Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38). CONCLUSIONS: Short-term CR for only 7d represents a preconditioning strategy that limits infarct size. It is associated with a unique gene and miR signature, including the activation of specific pro-survival kinases. These findings may have implications for therapeutic use of short-term CR. .
2015-05-08 | GSE68646 | GEO
Project description:How erythropoiesis responds to fasting remains to be explored. Here, Xu et al. showed that short-term intensive fasting promotes the production of red blood cells and boosts their functions by regulating MS4A3-CDK2 module to enhance megakaryocyte-erythroid progenitor self-renewal and erythroid-biased differentiation.
2023-01-02 | GSE200918 | GEO
Project description:Short-term depletion in Drosophila enteroendocrine cells
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Project description:Interventions: Bevacizumab was given over 30 min at the first time. If patients had no infusion reaction,the time was shortend to 10 min
Primary outcome(s): Progression free survival The rate of infusion reaction
Study Design: Single arm Non-randomized
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Project description:Effect of crude oil, dispersant and oil-dispersant mixtures on human intestinal microbiota
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Project description:Addictive drugs including opioids activate signal transduction pathways that regulate gene expression in the brain. However, changes in CNS gene expression following morphine exposure are poorly understood. We studied the effect of short- and long-term morphine treatment on gene expression in the hypothalamus and pituitary using genome-wide DNA microarray and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analyses. In the hypothalamus, we found that short-term morphine administration up-regulated (at least 2-fold) 39 genes and down-regulated six genes. Long-term morphine administration up-regulated 35 genes and down-regulated 51 hypothalamic genes. In the pituitary, we found that short-term morphine administration up-regulated (at least 2-fold) 110 genes and down-regulated 29 genes. Long-term morphine administration up-regulated 85 genes and down-regulated 37 pituitary genes. Strikingly, microarray analysis uncovered several genes involved in food intake (neuropeptide Y, agouti-related protein, and cocaine and amphetamine-regulated transcript) whose expression was strongly altered by morphine exposure in either the hypothalamus or pituitary. Subsequent RT-PCR analysis confirmed similar gene regulation of noteworthy genes in these regions. Finally, we found functional correlation between morphine-induced alterations in food intake and regulations of genes involved in this process. Changes in genes related to food intake may uncover new pathways related to some of the physiological effects of opioids. Keywords: Comparative treatment versus placebo 8 samples analyzed: 4 from hypothalamus (2 biological replicates and 2 dye swaps) and 4 from pituitary (2 biological replicates and 2 dye swaps) 8 samples analyzed: 4 from hypothalamus short term treatment (2 biological replicates and 2 dye swaps) and 4 hypothalamus long term treatment (2 biological replicates and 2 dye swaps)
2008-09-30 | E-GEOD-9525 | biostudies-arrayexpress