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| Status |
Public on Mar 23, 2024 |
| Title |
Chemo-senolytic therapeutic potential against angiosarcoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, one of the taxanes (genotoxic drugs), although it has a limited effect due to chemoresistance for prolonged treatment. Here we examine a new angiosarcoma treatment approach that combines chemotherapeutic and senolytic agents. We first find that the chemotherapeutic drugs, cisplatin and paclitaxel, efficiently induce cellular senescence of angiosarcoma cells. Subsequent treatment with a senolytic agent, ABT-263, eliminates senescent cells through the activation of the apoptotic pathway. In addition, expression analysis indicates that senescence-associated secretory phenotype (SASP) genes are activated in senescent angiosarcoma cells and that ABT-263 treatment eliminates senescent cells expressing genes in the type-I interferon (IFN-I) pathway. Moreover, we show that cisplatin treatment alone requires a high dose to remove angiosarcoma cells, whereas a lower dose of cisplatin is sufficient to induce senescence, followed by the elimination of senescent cells by senolytic treatment. This study sheds light on a potential therapeutic strategy against angiosarcoma by combining a relatively low dose of cisplatin with the ABT-263 senolytic agent, which can help ease the deleterious side effects of chemotherapy.
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| Overall design |
To understand how treatment with chemotherapeutic and senolytic agents affects gene expression in angiosarcoma cells, we performed RNA-seq analysis.
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| Contributor(s) |
Wang X, Chung CY, Yoshioka A, Hashimoto S, Jimbo H, Tanizawa H, Ohta S, Fukumoto T, Noma K |
| Citation(s) |
38570028 |
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| Submission date |
Oct 20, 2023 |
| Last update date |
Apr 04, 2024 |
| Contact name |
Hideki Tanizawa |
| E-mail(s) |
tanizawa@igm.hokudai.ac.jp
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| Phone |
011-706-5035
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| Organization name |
Hokkaido University
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| Department |
Institute for Genetic Medicine
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| Lab |
Division of Genome Biology
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| Street address |
Kita 15, Nishi 7, Kita-ku
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| City |
Sapporo |
| State/province |
Hokkaido |
| ZIP/Postal code |
060-8615 |
| Country |
Japan |
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| Platforms (1) |
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| Samples (13)
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| GSM7851421 |
MO-LAS-B cells, Cisplatin, rep2 |
| GSM7851422 |
MO-LAS-B cells, Paclitaxel, rep1 |
| GSM7851423 |
MO-LAS-B cells, Paclitaxel, rep2 |
| GSM7851424 |
MO-LAS-B cells, Cisplatin + ABT-263 |
| GSM7851425 |
ISO-HAS-B cells, Control, rep1 |
| GSM7851426 |
ISO-HAS-B cells, Control, rep2 |
| GSM7851427 |
ISO-HAS-B cells, Cisplatin, rep1 |
| GSM7851428 |
ISO-HAS-B cells, Cisplatin, rep2 |
| GSM7851429 |
ISO-HAS-B cells, Paclitaxel |
| GSM7851430 |
ISO-HAS-B cells, Cisplatin + ABT-263 |
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| Relations |
| BioProject |
PRJNA1030406 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE245935_RAW.tar |
2.9 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
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