RNAseq analysis of ruxolitinib treated breast cancers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107000 | GEO | 2018/11/05
REPOSITORIES: GEO
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Project description:RNAseq analysis of ruxolitinib treated breast cancers
| PRJNA418761 | ENA
Project description:We conducted a randomized phase II study with nested window-of-opportunity in patients with TN-IBC. Patients were randomized to receive a 7-day run-in of ruxolitinib (RUX) alone or ruxolitinib plus paclitaxel (RUX+PAC) in a 1:2 ratio, followed by 12 weeks of neoadjuvant paclitaxel alone or in combination with ruxolitinib in a 1:2 ratio. All patients subsequently received 4 cycles of doxorubicin plus cyclophosphamide, followed by modified radical mastectomy. Patients provided tumor tissue from research biopsies performed at baseline (pre-run-in) and after the completion of run-in therapy. Tumor tissue was evaluated for phosphorylated STAT3 (pSTAT3) using immunohistochemistry (IHC) and immunofluorescence, and a subset of cases were also analyze by RNA-seq. The primary objective was to evaluate the percent of patients whose tumors were pSTAT3-positive at baseline, and which subsequently became pSTAT3-negative after run-in therapy. Secondary endpoints included pathologic complete response (pCR), residual tumor burden (RCB) and event-free survival (EFS) from the date of surgery. There were 23 patients enrolled, 11 in RUX and 12 in RUX+PAC combination. The most common adverse events were fatigue and nausea. Two patients achieved pCR and 21 completed pre-operative therapy. We detected a decrease in pSTAT3 and IL6/JAK/STAT3 signaling pathways in post-run-in biopsies of RUX-treated samples, but this did not correlate with pCR, while RUX+PAC upregulated IL6/JAK/STAT3 signaling. Both treatments decreased GZM+ T cells implying immune suppression, which might have contributed to lack of efficacy.
2024-02-07 | GSE232764 | GEO
Project description:Transplant recipients of IDH2-R140Q JAK2-V617F expressing bone marrow were treated with AG221 and ruxolitinib monotherapy, combined therapy, or vehicle. LSKs were sorted from terminal samples and sequenced with three WT controls.
2018-02-22 | GSE95771 | GEO
Project description:The purpose of this study is to provide continued supply of ruxolitinib alone, ruxolitinib plus background cancer therapy, or background cancer therapy alone to subjects from an Incyte-sponsored study of ruxolitinib that has reached its study objectives or has been terminated.
This study will also provide another mechanism for reporting adverse events related to study drug safety.
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Project description:Ruxolitinib is a Janus kinase 1/2 inhibitor (JAK1/2) that blocks signal transduction of interferon-gamma, a critical cytokine involved in the pathogenesis of cutaneous lichen planus (LP). In this prospective phase II study, we investigated the efficacy of topical ruxolitinib in cutaneous LP and performed transcriptomic analysis pre- and post-therapy. Twelve patients with cutaneous LP applied topical ruxolitinib twice daily for 8 weeks. Primary endpoints were change in total lesion count and modified Composite Assessment of Index Lesion Severity (mCAILS) score in index treated and untreated index control lesions at week 4. Total lesion count decreased by a median of 50 lesions (interquartile range 25, 723; p<0.001). mCAILS scores decreased by a mean difference of 7.6 (standard deviation 8.8, p=0.016) between index treated and control lesions. Type I and II interferon pathways were enriched in LP and responsive disease displayed downregulation of interferon-stimulated genes (ISGs). In this small pilot study, topical ruxolitinib was highly effective in the treatment of cutaneous LP. Transcriptomic analysis confirmed LP as an interferon-driven disease and downregulation of ISGs correlated with disease response.
2022-01-13 | GSE193351 | GEO
Project description:Two patients with alopecia areata were treated with systemic ruxolitinib. Skin biopsies were taken before starting treatment and 12 weeks after starting treatment. We used microarrays to assess changes in gene expression of affected skin before and after starting treatment Two patients with alopecia areata were recruited for our study. Skin biopsies of affected scalp were taken prior to starting treatment with oral ruxolinitib. Additional skin biopsies were taken 12 weeks after starting treatment. Scalp skin biopsies were taken from patients without alopecia areata for comparison. RNA was extracted, cDNA libraries were made and profiled on affymetrix microarray chips.
2014-08-17 | E-GEOD-58573 | biostudies-arrayexpress
Project description:Hemophagocytic lymphohistiocytosis is a cytokine storm syndrome characterized by the excessive activation of myeloid and T cells. In primary HLH (pHLH), disease pathophysiology is driven by CD8 T cells proliferation and IFNg production. Therefore, targeting IFNg has been a viable option for the treatment of HLH. Since many cytokines that signaling throught the JAK/STAT pathway, including IFNg, largely drive cytokine storm in HLH, we and others have demonstrated that targeting JAK1/2 with ruxolitinib is effective in ameliorating disease manifestations in pre-clinical models of HLH. Both IFNg and ruxolitinib treatments have also shown great efficacy in dampening inflammation in patients with HLH, albeit not completely. Since ruxolitinib treatment does not fully inhibit IFNg production, we sought to determine the effect of combining ruxolitinib treatment with IFNg neutralization as a treatment option in a LCMV-infected Prf1 mice. We aimed to elucidate the effects of these treatments on the main hematologic and cellular parameters of disease. Moreover, we determined the main changes in the transcriptional landscape on CD8 T cells isolated from mice infected with LCMV either untreated or treated with aIFNg, ruxolitinib, or combination treatments. We demonstrate that combination treatment was very effective in reversing anemia and thrombocytopenia, but failed to reduce splenomegaly, hypercytokinemia, and myeloid and T cell numbers compared to ruxolitinib treatment. Transcriptional analysis revealed distinct pathways targeted by aIFNg and ruxolitinib; while aIFNg was more effective in downregulating the expression of interferon gamma response genes, allograft rejection, and complement genes, ruxolitinib treated CD8 T cells displayed a reduction in expression of genes involved in reactive oxygen species, glycolysis, E2F targets, and protein secretion pathways. Therefore, this study provide novel insights on the effects of combining ruxolitinib treatment with IFNg neutralization in the treatment of primary HLH.
2023-04-24 | GSE218500 | GEO
Project description:Gene expression profiling of CMS4 colon cancer treated with Imatinib in the ImPACCT study. Fresh-frozen biopsies were taken during diagnostic colonoscopy for CMS4 identification. Five patients gave informed consent for two week of neoadjuvant Imatinib therapy prior to removal of the primary tumor. Fresh-frozen samples were taken from surgically resected colon cancer specimens.
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Project description:We report the effect of rexolitinib on neutrophil function, by extracting mouse bone marrow neutrophils, and after treatment with Ruxolitinib and vehicle, extracting neutrophil RNA from each group for RNA-seq. Finally, we show that Ruxolitinib produces functional effects on neutrophils mainly through inflammatory signaling pathways, amplifying the immune effects of neutrophils in an inflammatory environment and accelerating neutrophil death.
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Project description:Copy number alteration (CNA) is a good signpost to identify cancer related genes. CNAs were analyzed using the Agilent 244K array comparative genomic hybridization (aCGH) in fresh-frozen tumor and matched normal tissues from 10 gastric cancer patients.
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