1.
Double-Sided Personality: Effects of Arsenic Trioxide on Inflammation.
Zhang, J, Zhang, Y, Wang, W, Li, C, Zhang, Z
Inflammation. 2018;(4):1128-1134
Abstract
In 1992, arsenic trioxide (As2O3, ATO) was demonstrated to be an effective therapeutic agent against acute promyelocytic leukemia (APL), rekindling attention to ATO applications in U.S. Food and Drug Administration clinical trials for the treatment of cancers, such as leukemia, lymphomas, and solid tumors. ATO is a potent chemotherapeutic drug that can also be used to treat other diseases, such as autoimmune diseases, because it affects multiple pathways including apoptosis induction, differentiation stimulation, and proliferation inhibition. As inflammation is a critical component of disease progression, ATO is a feasible treatment option based on its ability to protect against inflammation. However, ATO is also a well-known carcinogen because of its pro-inflammatory effect. This review will focus on the double-sided effects of ATO on inflammation as well as the relevant mechanisms underlying these effects, aiming to provide a rational understanding of how ATO effects the immune system. We especially aim to provide a comprehensive overview of our current knowledge of how ATO influences inflammation.
2.
Arsenic speciation in the phloem exudates of rice and its role in arsenic accumulation in rice grains.
Ye, W, Zhang, J, Fan, T, Lu, H, Chen, H, Li, X, Hua, R
Ecotoxicology and environmental safety. 2017;:87-91
Abstract
Arsenic (As) speciation in the phloem sap of rice plants and its role in As accumulation in rice grains remain largely uncharacterized. In the present study, we tested As chemical species in the phloem exudates of rice treated with arsenate [As(V)], arsenite [As(III)], monomethylarsonic acid [MMA(V)], or dimethylarsinic acid [DMA(V)]. As(V) was the main species (58%) in the phloem exudates of As(V)-exposed rice, whereas As(III) predominated (69%) in As(III)-exposed rice. A large proportion of As(V) (41-45%) was observed in the phloem exudates when rice was treated with methylated As species. High concentrations of phytochelatins were detected in the phloem exudates when the As(V) treatment level was increased. The role of phloem transport was analyzed by applying a ±stem-girdling treatment to the rice plants, limiting phloem transport to the grain in rice pulsed with As(III), As(V), MMA(V), or DMA(V). The findings of the present study indicate that organic As is more mobile than inorganic As during phloem transport. Phloem transport accounted for 54% of As(III), 56% of As(V), 100% of MMA(V), and 89% of DMA(V) transport to the grain. The total As concentration and As(III) percentage in rice phloem and grain were significantly affected by increasing the phosphate concentration in the medium.
3.
Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy.
Zhou, GB, Zhang, J, Wang, ZY, Chen, SJ, Chen, Z
Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2007;(1482):959-71
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Abstract
To turn a disease from highly fatal to highly curable is extremely difficult, especially when the disease is a type of cancer. However, we can gain some insight into how this can be done by looking back over the 50-year history of taming acute promyelocytic leukaemia (APL). APL is the M3 type of acute myeloid leukaemia characterized by an accumulation of abnormal promyelocytes in bone marrow, a severe bleeding tendency and the presence of the chromosomal translocation t(15;17) or variants. APL was considered the most fatal type of acute leukaemia five decades ago and the treatment of APL was a nightmare for physicians. Great efforts have been made by scientists worldwide to conquer this disease. The first use of chemotherapy (CT) was unsuccessful due to lack of supportive care and cytotoxic-agent-related exacerbated coagulopathy. The first breakthrough came from the use of anthracyclines which improved the complete remission (CR) rate, though the 5-year overall survival could only be attained in a small proportion of patients. A rational and intriguing hypothesis, to induce differentiation of APL cells rather than killing them, was raised in the 1970s. Laudably, the use of all-trans retinoic acid (ATRA) in treating APL resulted in terminal differentiation of APL cells and a 90-95% CR rate of patients, turning differentiation therapy in cancer treatment from hypothesis to practice. The combination of ATRA with CT further improved the 5-year overall survival. When arsenic trioxide (ATO) was used to treat relapsed APL not only the patients but also the ancient drug were revived. ATO exerts dose-dependent dual effects on APL cells: at low concentration, ATO induces partial differentiation, while at relatively high concentration, it triggers apoptosis. Of note, both ATRA and ATO trigger catabolism of the PML-RARalpha fusion protein which is the key player in APL leukaemogenesis generated from t(15;17), targeting the RARalpha (retinoic acid receptor alpha) or promyelocytic leukaemia (PML) moieties, respectively. Hence, in treating APL both ATRA and ATO represent paradigms for molecularly targeted therapy. At molecular level, ATRA and ATO synergistically modulate multiple downstream pathways/cascades. Strikingly, a clearance of PML-RARalpha transcript in an earlier and more thorough manner, and a higher quality remission and survival in newly diagnosed APL are achieved when ATRA is combined with ATO, as compared to either monotherapy, making APL a curable disease. Thus, the story of APL can serve as a model for the development of curative approaches for disease; it suggests that molecularly synergistic targeted therapies are powerful tools in cancer, and dissection of disease pathogenesis or anatomy of the cancer genome is critical in developing molecular target-based therapies.