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.
A protein A modified Au-graphene oxide composite as an enhanced sensing platform for SPR-based immunoassay.
Zhang, J, Sun, Y, Wu, Q, Zhang, H, Bai, Y, Song, D
The Analyst. 2013;(23):7175-81
Abstract
A sensitive and selective wavelength modulation surface plasmon resonance (SPR) biosensor is reported with Au nanoparticle decorated graphene oxide (GO) as an enhanced sensing platform. GO sheets possess favourable water dispersibility, good biocompatibility and high loading capacity. An Au-GO composite with the Au spheres size of 15-20 nm was synthesized and modified with staphylococcal protein A (SPA). The as-prepared composite assembles directly onto the Au film surface of the SPR sensor. Meanwhile, SPA specifically recognizes and binds the Fc portion of antibodies, contributing to highly oriented antibody immobilization on the chip surface without any antibody modification. Consequently, the biosensor based on the SPA modified Au-GO composite exhibits a satisfactory response to rabbit IgG in the concentration range of 0.1-50 μg mL(-1), while the biosensor based on the sole SPA layer for antibody immobilization shows a response in the concentration range of 1.6-50 μg mL(-1). Experimental results show that the SPA modified Au-GO composite can be successfully used for the signal amplification of immunosensors, thereby improving the sensitivity and obviating the need of chemical modification of the antibody.
3.
Graphene oxide modified light addressable potentiometric sensor and its application for ssDNA monitoring.
Jia, Y, Yin, XB, Zhang, J, Zhou, S, Song, M, Xing, KL
The Analyst. 2012;(24):5866-73
Abstract
A light addressable potentiometric sensor (LAPS) is a kind of silicon based semiconductor sensor, and surface modification is a fundamental problem for its application in biological fields. Graphene oxide (GO) based biochemically activated LAPS were proposed, called GO-LAPS. The GO-LAPS were applied to monitoring single strand DNA (ssDNA) probe immobilization and its hybridization with complementary ssDNA molecules of different chain lengths (30, 21 and 14 base pairs, respectively). It was discovered that the curves of LAPS' currents versus analyte concentrations for ssDNA probe binding and the target ssDNA hybridization were different. Explanations were proposed based on the semiconductor's surface-electric-field-effect and the electrical properties of ssDNA molecule. Moreover, comparisons between GO-LAPS and LAPS without GO modification were carried out. Enhanced response currents of GO-LAPS were reported experimentally and analyzed theoretically based on X-ray photoelectron spectroscopy (XPS) of GO-LAPS. The limitation of target ssDNA monitoring was 1 pM to 10 nM, which suggested that this LAPS based platform could be developed as a sensitive means for short chain ssDNA detection.
4.
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.