MicroRNA Expression Profile of serum exosomes from Bortezomib-resistant and Bortezomib-response patients in multiple myeloma
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE71435 | GEO | 2016/07/31
SECONDARY ACCESSION(S): PRJNA291204
REPOSITORIES: GEO
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Project description:MicroRNA microarray profilling analysis was performed on exosomes derived from serum in patients with myeloma in two conditions of therapeutic efficacy, Bortezomib resistance and Bortezomib response. Bortezomib is approved and widely used treating myeloma. Two kinds of sample were analyzed. MicroRNA microarray profilling analysis (using miRCURY LNA microRNA Array, 7th generation REV - hsa, mmu & rno, mirBase release 18, ProductNumber=208520,208521,208522) was performed on exosomes derived from serum in patients with myeloma in two conditions of therapeutic efficacy, Bortezomib resistance and Bortezomib response.
2016-07-31 | E-GEOD-71435 | biostudies-arrayexpress
Project description:Gene expression profile (GEP) was analyzed from cultured bone marrow (BM) samples from patients with bortezomib responsive versus bortezomib resistant myeloma after 6-8 hours incubation in vitro with bortezomib 2 µg/ml or with PBS. Case D also had a fresh BM sample taken 75 minutes after IV injection of bortezomib.
2013-11-01 | GSE51940 | GEO
Project description:Multiple myeloma (MM) is a hematological malignancy worldwide in urgent need for novel therapeutic strategies. Since Velcade (bortezomib) was approved for the treatment of relapsed/refractory MM in 2003, we have seen considerable improvement in extending MM patient survival. However, most patients are fraught with high recurrence rate and incurability. Acupuncture is known for alleviating patient symptoms and improving the quality of life, but it is not well investigated in MM, especially in combination with bortezomib. In this study, we employed LC-MS and UHPLC-MS together with bioinformatics methods to test blood samples from 5TMM3VT MM murine model mice with four different treatments (control (C) group, bortezomib (V) treatment group, acupuncture (A) group and combined (VA) group). MM mice in group VA had longer survival time than mice in group A or group V. Joint pathway analysis indicated the underlying arginine and proline metabolism pathway among the 32 significantly decreased metabolites in group VA. CCK-8 assay and in vivo experiments validated that ornithine, the metabolite of arginine, promoted MM cell proliferation. In addition, gene expression omnibus (GEO) database analysis suggested that MM patients with higher ornithine decarboxylase 1 (ODC1) expression were evidently associated with poor overall survival. In summary, this study demonstrates the synergistic effects of acupuncture and bortezomib on extending the survival of MM model mice and provides potential therapeutic targets in the treatment of MM.
2022-02-21 | MTBLS3487 | MetaboLights
Project description:Bortezomib therapy has been proven successful for the treatment of relapsed and/or refractory multiple myeloma (MM). However, both intrinsic and acquired resistance has already been observed. In this study, we explored the relationship between CD9 expression and bortezomib sensitivity in MM Both intrinsic and acquired resistance has already been observed. In this study, we explored the relationship between CD9 expression and bortezomib sensitivity in MM. We found that down-regulation of CD9 by methylation decreased bortezomib sensitivity in multiple myeloma.
2014-03-13 | GSE55818 | GEO
Project description:RNA was extracted from myeloma cell lines which were made engraftable and resistant to bortezomib and the transcriptome was characterised using RNA sequencing.
2023-12-10 | GSE235288 | GEO
Project description:Among the blood cancers, 13% mortality is caused by Multiple myeloma (MM) type of haematological malignancy. In spite of therapeutic advances in chemotherapy treatment, still MM remains an incurable disease is mainly due to emergence of chemoresistance. At present time, FDA approved bortezomib is the first line drug for MM treatment. However, like other chemotherapy, MM patients are acquiring resistance against bortezomib. The present study aims to identify and validate bortezomib resistant protein targets in MM using iTRAQ and label free quantitative proteomic approaches. 125 differentially expressed proteins were commonly found in both approaches with similar differential expression pattern. XPO1 protein was selected for further validation as its significant high expression was observed in both iTRAQ and label free analysis. Bioinformatic analysis of these common differentially expressed proteins showed a clear cluster of proteins such as SMC1A, RCC2, CSE1, NUP88, NUP50, TPR, HSPA14, DYNLL1, RAD21 and RANBP2 being associated with XPO1. Functional studies like cell count assay, flow cytometry assay and soft agar assay proved that XPO1 knock down in RPMI 8226R cell line results in re-sensitization to bortezomib drug
2019-09-09 | PXD013859 | Pride
Project description:The combination of bortezomib and dexamethasone should become the reference induction treatment for multiple myeloma patients younger than 65 years. Pharmacogenomic profiles of genes involved in response to treatment may help to understand resistance. We performed gene expression profiling in 9 myeloma cell lines, incubated or not with bortezomib and dexamethasone for 6 hours. Supervised analysis identified significantly up regulated genes involved in stress responses. We focused on REDD1 a gene known to be rapidly induced by a wide variety of stress conditions and DNA damages. REDD1 expression was early and highly induced after bortezomib exposure. REDD1 induction was associated with the dephosphorylation of P70 S6 ribosomal kinase (P70S6K), a key substrate of mTOR. These effects were dependent upon cell line. REDD1 was overexpressed within two hours in bortezomib resistant cell lines in association with a cell size decrease. In sensitive cell lines, neither REDD1 induction nor morphological changes occurred. RNA interference mediated inhibition of REDD1 induction abrogates P70S6K dephosphorylation, early transitory cell size reduction and enhances sensitivity to bortezomib - dexamethasone. Our results suggest that mTOR regulation could be a resistance mechanism mediated by REDD1 expression in myeloma cells. Nine cell lines of multiple myeloma studied, incubated or not with bortezomib and dexamethasone, examined with spotted cDNA nylon membrane. Cell line and Code : JJN3 = Vel_1x; L363 = Vel_2x; LP1 = Vel_3x; MDN = Vel_4x; NCI = Vel_5x; RPMI = Vel_6x; SBN = Vel_7x; U266 = Vel_8x; XG1 = Vel_9x.
2010-02-14 | E-GEOD-11866 | biostudies-arrayexpress
Project description:Bortezomib therapy has been proven successful for the treatment of relapsed and/or refractory multiple myeloma (MM). However, both intrinsic and acquired resistance has already been observed. In this study, we explored the relationship between CD9 expression and bortezomib sensitivity in MM Both intrinsic and acquired resistance has already been observed. In this study, we explored the relationship between CD9 expression and bortezomib sensitivity in MM. We found that down-regulation of CD9 by methylation decreased bortezomib sensitivity in multiple myeloma. A six chip study using total RNA recovered from three separate wild-type cultures of U266 cells and three separate cultures of U266 with CD9 overexpression. Each chip measures the expression level of 45,033 genes from Homo sapiens with fourteen 60-mer probe pairs (PM/MM) per gene, with three-fold technical redundancy.
2014-03-13 | E-GEOD-55818 | biostudies-arrayexpress
Project description:The combination of bortezomib and dexamethasone should become the reference induction treatment for multiple myeloma patients younger than 65 years. Pharmacogenomic profiles of genes involved in response to treatment may help to understand resistance. We performed gene expression profiling in 9 myeloma cell lines, incubated or not with bortezomib and dexamethasone for 6 hours. Supervised analysis identified significantly up regulated genes involved in stress responses. We focused on REDD1 a gene known to be rapidly induced by a wide variety of stress conditions and DNA damages. REDD1 expression was early and highly induced after bortezomib exposure. REDD1 induction was associated with the dephosphorylation of P70 S6 ribosomal kinase (P70S6K), a key substrate of mTOR. These effects were dependent upon cell line. REDD1 was overexpressed within two hours in bortezomib resistant cell lines in association with a cell size decrease. In sensitive cell lines, neither REDD1 induction nor morphological changes occurred. RNA interference mediated inhibition of REDD1 induction abrogates P70S6K dephosphorylation, early transitory cell size reduction and enhances sensitivity to bortezomib - dexamethasone. Our results suggest that mTOR regulation could be a resistance mechanism mediated by REDD1 expression in myeloma cells.
2010-02-15 | GSE11866 | GEO
Project description:The aims of this study were to assess the feasibility of prospective pharmacogenomics research in multicenter international clinical trials of bortezomib in multiple myeloma and to develop predictive classifiers of response and survival with bortezomib. Patients with relapsed myeloma enrolled in phase 2 and phase 3 clinical trials of bortezomib and consented to genomic analyses of pretreatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were used for gene expression profiling using DNA microarrays. Data quality and correlations with trial outcomes were assessed by multiple groups. Gene expression in this dataset was consistent with data published from a single-center study of newly diagnosed multiple myeloma. Response and survival classifiers were developed and shown to be significantly associated with outcome via testing on independent data. The survival classifier improved on the risk stratification provided by the International Staging System. Predictive models and biologic correlates of response show some specificity for bortezomib rather than dexamethasone. Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents. Experiment Overall Design: Purified myeloma samples were collected prior to enrolment in clinical trials of bortezomib (PS-341). Samples were subject to replicate gene expression profiling using the Affymetrix 133A/B microarray. Data was normalized in MAS5.0 and the median of replicates is reported. Data was normalized to a Ttimmed mean of 15o and is NOT log transformed. Various patient parameters are reported as well as response, TTP and survival upon treatment with bortezomib or dexamethasone.
2008-06-17 | E-GEOD-9782 | biostudies-arrayexpress