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Cancer
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Elyce Cardonick, Charlotte Maggen, Puja Patel
Patients can present with DIC. All trans-retinoic acid, ATRA, is an important component of therapy to control DIC in APL and has been safely used during pregnancy [78–80]. ATRA is given with daunorubicin. The response seen with ATRA alone versus with daunorubicin is not significant, however, it may impact relapse rate. Being similar to retinoid, ATRA is contraindicated during the first trimester. A serious side effect of ATRA is differentiation syndrome (unexplained fever, respiratory distress due to capillary leak) and is treated with steroids. Arsenic trioxide, also used with ATRA in non-pregnant women, is also teratogenic during first trimester. There are limited case reports of safe use of arsenic in the second and third trimesters [81–83].
PML/RARα Fusion Gene and Response to Retinoic Acid and Arsenic Trioxide Treatment
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Alicja M. Gruszkaa, Myriam Alcalay
Arsenic trioxide, a naturally occurring chemical element, found in both organic and inorganic compounds, is a poison-become-medicine used for more than 2000 years [59]. Arsenic affects many cellular pathways through different targets. The interaction of trivalent arsenic with the thiol (-SH) groups of cysteine-rich proteins constitutes the basic reaction that underlies the its biological actions [20]. Arsenic promotes degradation of normal PML, as well as the destruction of the PML/RARa fusion protein through its PML moiety. It has been recently shown that arsenic binds directly to -SH groups of PML and generates reactive oxygen species (ROS). The RBCC domain of the PML protein contains cysteine-rich zinc fingers (ZFs) that in normal conditions bind atoms of zinc. The interaction of the ZFs with arsenic leads to slight changes in their structure ultimately causing oligomerisation of PML proteins. Arsenic binds to the cysteine residues of ZFs within the same molecule or by forming ROS-induced disulphide-links with the RBCC domains in the homodimer, facilitating further oligomerisation of PML and PML/RARa. The resultant multimers form matrix-associated NBs that are subsequently SUMOylated by UBC9 enzyme followed by RNF4 ubiquitin E3 ligase-mediated ubiquitination and proteasomal degradation [29, 63] (Fig. 10.1).
Risk Characterization
Published in Ted W. Simon, Environmental Risk Assessment, 2019
Arsenic is a naturally occurring metal widely distributed in soil and rock. Arsenic compounds have been used for years as pesticides, wood preservatives, and as alloy material for automobile batteries and electronic parts. During Victorian times, arsenic trioxide, or “white arsenic,” was used as a cosmetic. At that time and others in history, arsenic compounds were used to treat parasitic infections and syphilis. Dating from the late 1800s, arsenic trioxide in the form of Fowler’s solution was used to treat leukemia and psoriasis. In 2000, the US Food and Drug Administration approved arsenic trioxide for treatment of acute promyelocytic leukemia.102
Clinical characteristics of a patient with de novo acute promyelocytic leukemia with JAK2 v617f mutation
Published in Hematology, 2022
Yi-zhi Jiang, Zhong-ling Wei, Na-na Wang, Chen Huang, Jun Huang, Jia-wei Yan, Ran Wang, Zheng-zhi Yu, Dong-ping Huang
The patient was immediately treated with oral ATRA (20 mg/m2/day) and intravenous arsenic trioxide (ATO, 0.16 mg/kg/day) (Figure 2). Daunorubicin and cytarabine were used as a cytoreductive therapy. However, after three days of treatment, her WBC count began to increase rapidly, reaching as high as 36.5 × 109/L on day 7. A diagnosis of differentiation syndrome was made, which was successfully managed with treatments of dexamethasone and other supportive measures. She became PCR negative for PML/RARα after achievement of CR at two months with the completion of dual induction chemotherapy. The patient was then put on consolidation chemotherapy with daunorubicin/harringtonine and cytarabine for a total of three cycles. She continued ATRA and ATO treatment throughout consolidation.
Intravenous As2O3 as a promising treatment for psoriasis — an experimental study in psoriasis-like mouse model
Published in Immunopharmacology and Immunotoxicology, 2022
Xiaoji Hao, Xiaohui Liu, Shunfei Yu, Chang Qin, Ruonan Wang, Chunna Li, Jing Shao
Medications containing arsenic have been widely studied in the treatment of psoriasis. Arsenic trioxide (As2O3) is known to inhibit the proliferation and promote apoptosis of various tumor cells [20]. Intravenous As2O3 (10 mg/kg⋅bw for adult; 0.16 mg/kg⋅bw for infant) has been established as a standardized regimen for acute promyelocytic leukemia (APL) with safety approval [21–23]. Previously, we observed that treatment protocols containing As2O3 on APL associated with psoriasis have greatly improved skin conditions while achieving clinical remission in APL, consistent with clinical observations by others [24]. This finding brought us into this effort for identifying the molecular basis underlying the efficacy of As2O3 on psoriasis. We hypothesized that As2O3 treatment of psoriasis may be achieved by regulating the RIG-I-directed downstream signaling pathways for improvement and optimization of keratinocyte proliferation and differentiation.
Analysis of gamma-glutamyltransferase in acute promyelocytic leukemia patients undergoing arsenic trioxide treatment
Published in Hematology, 2021
Meijuan Sui, Hong Wei, Qian Zhang, Ruolin Xiu, Xiaohan Shen, Zhuo Zhang, Jin Zhou
Arsenic trioxide (As2O3, ATO) was firstly used for the treatment of acute promyelocytic leukemia (APL) patients in the First Affiliated Hospital, Harbin Medical University in 1970s. ATO is a striking medication for patients with APL, even in relapsed APL patients, more than 90% achieved complete remission (CR) [1,2]. However, ATO has some toxic effects and is accompanied by a serious of side effects in a small number of patients [3–5]. Concerns have been raised about the hepatotoxicity in APL patients treated with ATO [6]. Elevated gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) are generally observed. Hepatotoxicity was observed in 65.5% of APL patients treated with single-agent ATO, especially during the induction phase. Increased liver enzymes levels were the major manifestations of hepatotoxicity [6,7]. It has been reported that ALT and AST in the early stage of ATO treatment were significantly higher than the beginning, but the elevated values dramatic decline following the treatment [6]. Generally, we thought that changes in ALT and AST were indicators of liver injury [8]. But, GGT is not considered as main indicator of liver injury. GGT may be associated with WBC [9–11]. Whether definite relations existed among GGT, ALT and AST?