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Artesunate overcomes the resistance of basal type of bladder cancer to RC48

ABSTRACT: ERBB2 expression mediates sensitivity of bladder cancer cells to RC48. JAK/STAT3 pathways compensatory activation after exposing RC48. A combination of STAT3 inhibitor-artesunate and RC48 could significantly inhibit basal bladder cancer growth. These findings provided a theoretical foundation for subsequent individualized therapy for MIBC based on the molecular types.

ORGANISM(S): Homo sapiens

PROVIDER: GSE237789 | GEO | 2024/06/01

REPOSITORIES: GEO

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Differential Gene expression anslysis between artesunate sensitive and resistat Leishmania donovani

Project description:Gene expression analysis was carried out between experimental artesunate resistant Leishmania donovani (adapted to 50 µM artesunate drug pressure) and it's corresponding wild type artesunate sensitive parasite.

2019-08-30 | GSE118460 | GEO

Exploring the molecular mechanism of artesunate intervening in glioma based on DNA methylation sequencing technology

Project description:Whole gene methylation profiles of U87 and U251 glioma cells before and after artesunate treatment, Infinium MethylationEPIC BeadChip, samples including 3 U87 cell normal group, 3 U251 cell normal group, 3 artesunate treated U87 cell group, U251 cell group was treated with 3 artesunate.

2022-10-18 | GSE215784 | GEO

Transcription profiling of Plasmodium falciparum synchronized blood stages exposed to lethal doses of artesunate

Project description:Each experiment consisted in an artesunate-free culture (control) and an artesunate treated culture. For each time point explored, cDNA from parasites with and without the drug were labeled with different cyanines, mixed and hybridized. To analyse dynamic transcriptome alterations, two pilot experiments were performed in which RNA was harvested at 90 and 180 minutes of incubation with the drug. <br><br> Since artesunate is active on ring stages as well as on older trophozoite stages, we decided to explore different time points along the erythrocytic cycle and search for genes affected at each time point. Therefore, five drug treatment experiments, staggered between 20 hours and 30 hours of parasite development, were performed for the comparison of drug versus no drug at 90 minutes and 3 hours. <br><br> Different expression levels in artesunate-exposed vs. control unexposed cultures could reflect the added effects of the actual response to artesunate together with a possible difference in growth rate/developmental stage. To identify the developmentally regulated genes in the artesunate-free control culture, the 3 hours RNA was hybridized against the time 0 RNA (3 control experiments).

2008-06-01 | E-MEXP-1435 | biostudies-arrayexpress

Artesunate inhibits the cell viability of diffuse large B cell lymphoma cells by increasing the susceptibility to ferroptosis (RNA-seq).

Project description:Comparing the effects of artesunate versus DMSO in three DLBCL cell lines, we found a decrease in cell viability to 80%-60%. Over increasing artesunate dosage,we found increasing ROS generation and lipid peroxidation. In combination with the Ferrostatin-1 rescue experiment, we conclude that cell death induced by artesunate is ferroptotic. We compared the transcriptome of the U2932 cell line with and without 100µm artesunate in triplicate. A ferroptosis gene signature is shown to be enriched among the upregulated genes of this comparison. GPX4 protein expression was shown to be downregulated after artesunate in U2932 cells, but not in the rescue experiment with Ferrostatin-1. MT1G gene expression was identified as required for artesunate-mediated ferroptosis via targeted suppression by shRNAs. We present significantly decreased cell viability when combining artesunate with doxorubicin, suggesting a potential translation into clinic for treatment of ABC and GCB DLBCL.

2024-03-06 | GSE260741 | GEO

APIM-peptide targeting PCNA improves cisplatin therapy in a rat muscle-invasive bladder cancer model

Project description:High mortality rate of muscle-invasive bladder cancer (MIBC) and complexity of disease demand new multi-targeting treatment strategies. Targeting proliferating cell nuclear antigen (PCNA) with a peptide containing the AlkB homologue 2 PCNA interacting motif (APIM), is shown to impair multiple vital cellular stress responses and induce hypersensitivity against several chemotherapeutics in different pre-clinical models. This study examine the anti-cancer efficacy of the novel APIM-peptide drug when combined with cisplatin-based therapies (cisplatin, cisplatin/gemcitabine (GC) and methotrexate/vinblastine/adriamycin/cisplatin (MVAC)) in a panel of bladder cancer (BC) cells and with intravenous cisplatin-therapy in a rat MIBC-model. Furthermore, we explore the molecular mechanisms underlying the observed effects on a genomic, proteomic and metabolomic level using microarray, multiplexed inhibitor bead (MIB)-assay, and targeted mass spectrometric metabolite profiling. The APIM-peptide significantly increased the efficacy of all cisplatin-based therapies in all BC cell lines tested, including a cisplatin resistant cell line and reduced the tumor load in cisplatin treated MIBC-bearing rats. Genome and proteome analysis of APIM-peptide/cisplatin treated BC cells revealed reduced expression of multiple proteins frequently overexpressed in MIBC. Of notice, the EGFR/ERBB2, PI3K/Akt and MAPK signaling pathways and anti-apoptosis were downregulated. We suggest that the anti-cancer effect of the APIM-peptide is through the downregulation of several known oncogenic signaling pathways including anti-apoptosis. Together our results indicate that the APIM-peptide represents a potential improved treatment approach for patients with MIBC.

2018-09-10 | PXD008724 | Pride

Artesunate shows potent anti-tumor activity in B-cell lymphoma by inducing ER-stress response

Project description:Artesunate shows potent anti-tumor activity in B-cell lymphoma by inducing ER-stress response

2017-02-07 | GSE94553 | GEO

Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer

Project description:Background: Bladder-sparing trimodality therapy (TMT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), and biomarkers to inform therapy selection are needed. Objective: To evaluate immune and stromal signatures in MIBC treated with TMT.

2019-03-23 | GSE128701 | GEO

RNA-seq analysis of the mouse brain reveals inflammatory genes associated with early artesunate treatment of experimental cerebral malaria

Project description:Purpose:This study aimed to investigate the transcriptome-wide response of experimental cerebral malaria (ECM) and artesunate treated mice brain on 6 days post-infection. Methods: C57BL/6 mice were infected with Plasmodium berghei ANKA to construct a murine ECM in MB and AB group. AB group treated with artesunate (30mg/kg), while CB group treated with PBS for 4 days. Mice brain was tested by RNA-seq. Results: Gene ontology and KEGG pathway analyses of differentially expressed genes (DEGs) were performed. quantitative reverse transcription polymerase chain reaction (qPCR) verify DEGs such as Il6, Il1b, Il10, Tnf, Ifng, Il21, Icam1, which were up-regulated in MB vs. CB, while down-regulated in AB vs. MB. Conclusions:Our study revealed a transcriptome-wide profile in ECM and artesunate treated mice brain, and help to explore the underlying mechanism, as well as the further development of therapeutic strategies for clinical cerebral malaria.

2022-12-02 | GSE162535 | GEO

Patient-derived primary xenografts in the preclinical development of novel targeted therapies for bladder cancer

Project description:Purpose: While molecular targeted therapy has revolutionized the treatment of many cancers, little progress has been made in the development of novel therapies for muscle invasive bladder cancer (MIBC). Here we report on the establishment and characterization of patient-derived primary MIBC xenografts Tumor fragments derived from 7 patients with MIBC were grafted under the renal capsule of NOD-SCID mice and subsequently transplanted to further mice over multiple generations. Patient tumor and xenograft tissue were processed for analysis of , gene expression by microarray, and expression of select potential target pathways by immunohistochemistry (IHC).

2015-03-27 | E-GEOD-67312 | biostudies-arrayexpress

Expression data from bladder tumors and adjacent normal tissues

Project description:miRNAs are involved in cancer development and progression,acting as tumor suppressors or oncogenes. Half of the human miRNAs are located in cancer-associated genomic regions and can function as tumor suppressor genes or oncogenes depending on their targets miRNA profiling was performed on paired bladder cancer tissues and differentially expressed miRNAs were identified in BC and adjacent noncancerous tissues of any disease stage/grade. Ten paired bladder cancer tissues (5 low-grade non-muscle-invasive bladder cancer[NMIBC] and 5 high-grade muscle-invasive bladder cancer[MIBC]) were sent to CapitalBio Corp. (Beijing) for noncoding RNA microarray analysis. The microarray analysis was done as described on the Web site of CapitalBio. NMIBC samples include 07A, 19A, 23A, 24A and T63 while coresponding pairs include 07B, 19B, 23B, 24B and 63. MIBC samples include 10A, 20A, 21A, 34A and 49A while coresponding pairs include 10B, 20B, 21B, 34B and 49B.

2012-07-06 | E-GEOD-39093 | biostudies-arrayexpress

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