Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute arsenic trioxide poisoning in mice

Abstract Background Microwave ablation (MWA) has become an alternative treatment for unresectable surgery for hepatocellular carcinoma (HCC), but it still faces the risk of recurrence and metastasis after treatment. Recent studies have found that miR-34a presents decreased gene expression in residual tumours after ablation therapy and can increase the therapeutic effect of arsenic trioxide on HCC, which brings new opportunities for its treatment. Methods A pH-sensitive charge inversion material was used to construct a nanotargeted delivery system that presents the synergistic effect of miR-34a and As2O3. We established in vitro and in vivo models of microwave ablation of HCC and performed in-depth research on dual drug systems to inhibit the rapid progression of HCC after microwave ablation in cell pyroptosis. Results The antitumour effect was enhanced with double-drug nanoparticles relative to a single formulation, and the therapeutic efficacy of the nanoparticles was more significant in a weakly acidic environment. Dual-drug nanoparticles could increase the N-terminal portion of GSDME, decrease the expression of Cyt-c and c-met. Conclusions Dual-drug nanoparticles may improve the therapeutic efficacy of HCC with insufficient ablation through Cyt-c and GSDME-N and decrease the expression levels of c-met. It is expected to provide new treatment methods for residual liver cancer after microwave ablation, prolong the survival of patients and improve quality of life.

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Vascular Disrupting Agent Arsenic Trioxide Enhances Thermoradiotherapy of Solid Tumors

Journal of Oncology ◽

10.1155/2012/934918 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Robert J. Griffin ◽

Brent W. Williams ◽

Nathan A. Koonce ◽

John C. Bischof ◽

Chang W. Song ◽

...

Keyword(s):

Arsenic Trioxide ◽

Solid Tumors ◽

Therapeutic Efficacy ◽

Vascular Disrupting Agent ◽

Vascular Disruption ◽

Control Tumor Growth ◽

Powerful Means ◽

Control Tumor ◽

Hypofractionated Radiation

Our previous studies demonstrated arsenic trioxide- (ATO-) induced selective tumor vascular disruption and augmentation of thermal or radiotherapy effect against solid tumors. These results suggested that a trimodality approach of radiation, ATO, and local hyperthermia may have potent therapeutic efficacy against solid tumors. Here, we report the antitumor effect of hypofractionated radiation followed by ATO administration and local 42.5 °C hyperthermia and the effects of cisplatin and thermoradiotherapy. We found that the therapeutic efficacy of ATO-based thermoradiotherapy was equal or greater than that of cisplatin-based thermoradiotherapy, and marked evidence ofin vivoapoptosis and tumor necrosis were observed in ATO-treated tumors. We conclude that ATO-based thermoradiotherapy is a powerful means to control tumor growth by using vascular disruption to augment the effects of thermal and radiation therapy.

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