Abstract 2417
Background
An atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive tumor of the central nervous system that generally occurs in children under three years of age. There is no effective chemotherapy in most AT/RT patients. Within a tumor, small subpopulation cells called cancer stem cells do not respond to or are resistant to conventional anticancer drugs. In previous our studies, we observed the expression of aldehyde dehydrogenase (ALDH), a stem cell marker in AT/RT cells. Based on this, we confirmed the anticancer effect using disulfiram (DSF) known as ALDH inhibitor. Herein, we have investigated the anticancer effect of DSF with cisplatin in order to improve the effectiveness of AT/RT treatment.
Methods
Patient-derived primary cultured cells and established cell lines were utilized in vitro experiments. The combination effects of DSF with cisplatin was confirmed by cell viability, flow cytometry, ELISA and immunofluorescence analysis. The mechanism was identified by western blot analysis. Tumor volumes and survival rates were analyzed via bioluminescence live imaging in an AT/RT orthotopic xenograft mouse model to verify in vivo therapeutic effects.
Results
Our results demonstrate the anticancer effects of the combination of DSF and cisplatin both in vitro and in vivo. The combined treatment significantly inhibited the cell viability and ALDH enzyme activity of all AT/RT cells. The combination of DSF and cisplatin has been shown to modulate C-jun and ATF3 protein expression and activate PARP to induce apoptosis much more effectively. Importantly, the combination of DSF with cisplatin resulted in decreased tumor volume and increased long-term survival rate in AT/RT animal models.
Conclusions
Our study suggests that combination therapy of DSF and cisplatin can be used as a novel treatment strategy for AT/RT, which is difficult to treat with conventional chemotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Grant from the Seoul National University Hospital Research Fund (04-2018-0280) and a grant from the National Research Foundation (NRF) of Korea (2017R1A2B2008422).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2459 - Does bevacizumab increase joint pain ? Preliminary results of BEVARTHRALGIA Study
Presenter: Vauleon Enora
Session: Poster Display session 1
Resources:
Abstract
4913 - Prostatic cancer androgen deprivation therapy and bone health in carcinoma prostate.
Presenter: Gouri Shankar Bhattacharyya
Session: Poster Display session 1
Resources:
Abstract
1352 - Patterns of care for patients with metastatic bone disease in solid tumors – a cross-sectional study (SAKK 95/16)
Presenter: Michael Mark
Session: Poster Display session 1
Resources:
Abstract
6002 - Infection-Related Mortality in Different Types of Cancers
Presenter: Mohamed Gouda
Session: Poster Display session 1
Resources:
Abstract
5643 - Survival Trends in Critically ill Oncology Patients: impact of patient’s eligibility to post-ICU chemotherapy
Presenter: Edith Borcoman
Session: Poster Display session 1
Resources:
Abstract
3097 - Development and validation of a multivariable prediction model for 6-month mortality in older cancer patients: the GeriAtrIc-Tumor Score of PrEdiction for Early Death (GAIT SPEED)
Presenter: Angeli Angeli
Session: Poster Display session 1
Resources:
Abstract
856 - A Longitudinal Tracking and Quantitative Assessment of Paclitaxel-Induced Peripheral Neurotoxicity
Presenter: Ayumu Matsuoka
Session: Poster Display session 1
Resources:
Abstract
1662 - Efficiency of controlled cryotherapy in prevention of chemotherapy induced peripheral neuropathy (CIPN)
Presenter: Trudi Schaper
Session: Poster Display session 1
Resources:
Abstract
2766 - The Validity of Evaluations for Chemotherapy-Induced Peripheral Neuropathy (CIPN)
Presenter: Teppei Yamada
Session: Poster Display session 1
Resources:
Abstract
5683 - Prevention of chemoradiation-related mucositis in patients with head and neck cancer using dexamethasone-based mouthwash: A phase II randomized double-blind, placebo-controlled study
Presenter: Naiyarat Prasongsook
Session: Poster Display session 1
Resources:
Abstract