Medical use of arsenic trioxide

Last updated
Arsenic trioxide
ATC code L01XX27
use during pregnancy category D
half-life92 hours
plasma protein bindinginsignificant
metabolism methylation
excretion through urine (60% within 8 days)
routes of administrationintravenous
Sample of arsenic trioxide in powder form Arsenic trioxide.jpg
Sample of arsenic trioxide in powder form

Medical use of arsenic trioxide refers to the use of arsenic trioxide (Latin : Arsenum trioxydatum, [1] also known as "arsenic") as an chemotherapeutic agent in the treatment of acute promyelocytic leukemia. Arsenic trioxide has orphan drug status [2] and is available as the pharmaceutical preparation Trisenox. When in contact with water, it forms arsenous acid, which is believed to be the biologically active substance.

Contents

The action of this substance involves inhibiting the proliferation of cancer cells and inducing their differentiation or apoptosis, although the exact mechanism of the drug's action is not fully understood. Arsenic, due to its toxic properties, had been used for centuries as an effective and virtually undetectable [3] poison for the senses. [4] In the 20th century, its anticancer properties were observed, but attempts at oral administration were unsuccessful. Only intravenous administration of the substance yielded positive results, particularly in the treatment of a rare form of cancer – acute promyelocytic leukemia. This therapy is introduced after failure of treatment with retinoids and chemotherapy. [5] The treatment is characterized by relative safety and few side effects. Research is ongoing to find other uses for the drug.

History

In the 18th century, William Withering discovered that arsenic trioxide, when used in small doses, exhibited therapeutic effects. [6] During the same period, Thomas Fowler prepared a 1% solution of arsenic and potassium carbonate, which was used to treat skin diseases (primarily psoriasis) until the 20th century. [7] An arsenic-based drug, arsphenamine, was also developed for the treatment of syphilis, synthesized by Paul Ehrlich, though it was eventually replaced by penicillin. [8] Arsenic compounds were widely used to treat various diseases in the 19th and early 20th centuries. [7] [9] [10]

The first reports of the anticancer activity of arsenic trioxide date back to 1878, when a report from Boston City Hospital described Fowler’s solution lowering leukocyte levels in the blood of two healthy individuals and one patient. [4] [11] Arsenic trioxide continued to be used in the treatment of leukemia until the introduction of radiotherapy. It made a resurgence in the 1930s when the first studies confirmed the high efficacy of arsenic trioxide in treating chronic myelogenous leukemia. [12]

In the late 1960s, physicians working at the Harbin Medical Academy in China were sent to a center focusing on traditional Chinese medicine, where they used a melanoma ointment, with arsenic as its main ingredient. At that time, the arsenal of anticancer drugs was limited, prompting doctors to experiment with arsenic. Early trials used oral administration, but it showed strong toxic effects. In March 1971, the first trials of intravenous arsenic began, which showed significantly lower toxicity. For many years, arsenic trioxide was administered to patients with various cancers, showing the best results in the treatment of acute promyelocytic leukemia. [13] More than half of the patients from the first trial in Harbin survived for five years, prompting further research across other centers in China, [14] [15] and eventually at the Sloan-Kettering Memorial Institute in New York. [16] The results of clinical trials were favorable enough that in 2000, the drug received FDA approval. [17]

Mechanism of action

Anti-apoptotic protein Bcl-2 (isoform 1) Bcl-2 protein.png
Anti-apoptotic protein Bcl-2 (isoform 1)
AIF factor - one of the "death proteins" AIF factor.png
AIF factor – one of the "death proteins"
APAF-1 - one of the "death proteins" (illustrated in relation to ATP) APAF1.png
APAF-1 – one of the "death proteins" (illustrated in relation to ATP)
Bak - one of the pro-apoptotic proteins Bak protein.png
Bak – one of the pro-apoptotic proteins
Bax - one of the pro-apoptotic proteins Bax protein.png
Bax – one of the pro-apoptotic proteins
Transcription factor NF-kB (illustrated in relation to DNA) NF-kB protein.png
Transcription factor NF-κB (illustrated in relation to DNA)
JNK kinase JNK kinase.png
JNK kinase

The mechanism of action of arsenic trioxide is complex and not fully understood. Generally, the drug inhibits the proliferation of cancer cells and induces their differentiation and/or apoptosis, which can occur in various ways depending on the involved organelles and biochemical processes. Arsenic trioxide induces apoptosis through:

The first of these pathways involves the binding of a ligand to a receptor located on the surface of the cell membrane. The interaction of these two entities leads to the activation of various genes and releases a cascade of proteins characteristic of the apoptosis process. [25]

Arsenic trioxide also interacts with mitochondria. One of the initial changes in their structure induced by the drug is the opening of megachannels and the release of so-called "death proteins", primarily cytochrome c, APAF-1 (apoptotic peptidase activating factor 1), AIF (apoptosis-inducing factor), Smac/DIABLO protein, and endonucleases from the intermembrane space of mitochondria into the cytosol. In the cytoplasm, a protein complex known as the apoptosome forms, which activates further processes leading to apoptosis. [26]

Regardless of whether apoptosis is induced externally or internally, it always involves caspases, whose activation irreversibly leads the cell down the path of programmed cell death. [27] [28] Additionally, apoptosis is regulated by proteins from the Bcl-2 family, which can act as either pro-apoptotic or anti-apoptotic factors. [29]

The cause of acute promyelocytic leukemia is the translocation of the gene encoding the retinoic acid receptor (RARα) from chromosome 17 to a location near the PML gene on chromosome 15. This leads to the fusion of genes and the production of the PML/RARα protein. [30] This protein inhibits differentiation and the death of the cells in which it is present. Arsenic trioxide, even at low concentrations, causes the degradation of PML/RARα, thereby partially restoring the differentiation of cancerous promyelocytes. [31]

Arsenic trioxide activates JNK (c-Jun N-terminal kinase), also known as stress-activated protein kinase, which belongs to the MAPK (mitogen-activated protein kinase) family. These enzymes play a crucial role in signal transduction within the cell. Under normal conditions, JNK is activated by the phosphorylation of threonine and tyrosine residues. [32] [33] However, studies on specific cell lines derived from patients with acute promyelocytic leukemia have demonstrated that this activation also occurs in response to arsenic trioxide. [34]

It seems that the activation of JNK leads to the phosphorylation of both anti-apoptotic proteins (Bcl-2, Bcl-Xl) and pro-apoptotic proteins – Bax (Bcl-2-associated X protein), Bak (Bcl-2 homologous killer), and Bid (BH3 interacting domain death agonist) – effectively activating them. Pro-apoptotic proteins contain the BH3 domain, which is responsible for their "death-inducing" activity. They cause the formation of ion channels in the mitochondrial membrane, resulting in the release of the aforementioned apoptotic factors into the cytoplasm. Anti-apoptotic proteins owe their function to a hydrophobic cleft in their spatial structure that binds to the BH3 domain, thereby neutralizing the effects of the "death" proteins. [35] Under normal conditions, the decision for a cell to undergo apoptosis depends on the ratio of pro-apoptotic to anti-apoptotic proteins. In the case of arsenic trioxide-induced apoptosis, two mechanisms play a significant role in increasing the levels of pro-apoptotic proteins. The first is related to the functioning of the transcription factor NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). NF-κB exists in the cytoplasm in an inactive state, in a complex with the specific reaction inhibitor IκB (IKK). This complex consists of two catalytic subunits – IKKα and IKKβ – and a regulatory unit IKKγ/NEMO. The phosphorylation and degradation of the inhibitor release NF-κB, which then translocates to the cell nucleus and activates genes responsible for producing "survival" proteins (such as p53, Bcl-2, and other inhibitors of apoptosis). NF-κB also protects cells from apoptotic stimulation involving the TNF-α receptor. Arsenic trioxide binds to the cysteine at position 179 of IKKβ, thus preventing the release of NF-κB. [35] The absence of this protein in the cytoplasm allows for the induction of apoptosis via the extrinsic pathway and activates caspases 3 and 8. [36]

This mechanism has been observed not only in acute promyelocytic leukemia cells and Hodgkin lymphoma but also in patients with myelodysplastic syndrome. [35] [37] [38] The second mechanism that increases the levels of pro-apoptotic proteins is the downregulation of bcl-2 gene transcription. [39] This effect has been observed in HL-60 and NB4 human leukemia cells. [40] [41]

In 2003, Japanese researchers discovered that arsenic trioxide induces apoptosis not only through the TNF-α receptor. Studies indicate that the drug also acts pro-apoptotically through the CD95 receptor, which affects the activation of caspases 8 and 3. [42] [43] In multiple myeloma cells, arsenic trioxide interacts with the APO2/TRAIL receptor, activating caspases 8 and 9. [44] [45]

Arsenic trioxide also affects the intracellular concentration of glutathione, which is a crucial component of the redox system (it removes radicals and reduces hydrogen peroxide). It also participates, along with peroxidase and catalase, in regulating the levels of reactive oxygen species. [46] Arsenic trioxide inhibits glutathione peroxidase, thereby decreasing its concentration in the cell, which leads to an increase in the levels of reactive oxygen species. [47] These, in turn, increase the permeability of the mitochondrial membrane, causing the release of apoptotic factors and initiating the apoptosis process. [48]

Additionally, arsenic trioxide degrades poly(ADP-ribose) polymerase, which, combined with the activation of caspases, inhibits DNA repair and halts the cell cycle. [49] The phase of the cell cycle at which the blockage occurs primarily depends on the p53 protein. In cells containing the so-called "wild type" (non-mutated) p53, the cell cycle is halted in the interphase, while in cells with mutated p53, it is halted in the G2/M phase. [44] [50]

Mechanism of action of arsenic trioxide. The illustration presents four main therapeutic pathways of arsenic trioxide: A - external apoptosis pathway, B - mitochondrial pathway, C - interaction of arsenic trioxide with Bcl-2 family proteins, D - impact of arsenic trioxide on the NF-kB transcription factor. Arsenic trioxide - mechanism of action.png
Mechanism of action of arsenic trioxide. The illustration presents four main therapeutic pathways of arsenic trioxide: A – external apoptosis pathway, B – mitochondrial pathway, C – interaction of arsenic trioxide with Bcl-2 family proteins, D – impact of arsenic trioxide on the NF-κB transcription factor.

Clinical studies

Arsenic trioxide was clinically tested in two open-label, single-arm trials without a control group, involving 52 patients with acute promyelocytic leukemia who had previously been unsuccessfully treated with anthracyclines and retinoids. The results of these studies are presented in the table below. [52] [53] [54]

StudySingle-center n=12Multi-center n=40
Dose of arsenic trioxide (mg/kg body weight/day)0.16 (median: 0.06–0.20)0.15
Complete remission11 patients (92%)34 patients (85%)
Average time to bone marrow remission32 days35 days
Average time to achieve complete remission54 days59 days
18-month survival rate67%66%
n – number of patients participating in the study

Studies have also been conducted on the effect of arsenic trioxide on other cancers. These showed that the drug also induces apoptosis in lung cancer cells (especially in combination with sulindac). [55] The efficacy of arsenic trioxide has also been demonstrated in the treatment of multiple myeloma, in combination with ascorbic acid [56] and bortezomib. [57]

Animal studies have shown that the drug also affects ovarian, [58] liver, stomach, [59] prostate, and breast cancers, [60] as well as gliomas [61] and pancreatic cancer (in combination with parthenolide). [62] However, attempts to use arsenic trioxide in the treatment of solid tumors have been limited by the drug's toxicity. [63]

Arsenic trioxide also appears promising for treating autoimmune diseases (based on studies in mice). [64]

Pharmacokinetics

Detailed pharmacokinetic studies on arsenic trioxide have not been conducted. When administered intravenously, a steady state is reached after 8–10 days. Arsenic binds to proteins to an insignificant extent. The highest concentrations of arsenic are found in the liver, kidneys, heart, lungs, hair, and nails. Arsenous acid is oxidized to arsenic acid and methylated in the liver, [65] [66] [67] and then excreted 60% in the urine. The drug has a half-life of 92 hours. Arsenic trioxide is neither a substrate nor an inhibitor of cytochrome P450 isozymes (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, 4A9/11). [68] [69]

Indications

Arsenic trioxide is intended for the induction of remission and consolidation in adult patients with acute promyelocytic leukemia who have the t(15;17) translocation and/or the PML/RARα gene. The drug should be used after treatment failure or relapse. Prior therapy should include retinoid and chemotherapy. [70]

Special warnings

To ensure the safe use of arsenic trioxide, the following precautions should be observed: [71]

Interactions

Arsenic trioxide is known to prolong the QT interval. If possible, medications that also prolong QT should not be used concurrently, including: [79] [80]

Prior use of:

increases the likelihood of torsades de pointes. [79] [80]

Side effects

Side effects were reported in 37% of patients treated with arsenic trioxide. However, these effects were generally mild and resolved during treatment. Patients tolerated consolidation therapy better than induction therapy. The most common side effects include: [81] [82] [83]

Severe adverse effects are relatively rare and include: [81]

Other side effects include allergic skin reactions (including reactions at the injection site, injection site pain), [65] gastrointestinal disturbances (diarrhea), various types of pain, visual disturbances, [84] and bleeding. [85] If the drug extravasates, local irritation and phlebitis may occur. [65]

Overdose

In the event of arsenic poisoning (manifesting as seizures, muscle weakness, confusion), [86] the administration of the drug should be immediately discontinued, and appropriate treatment should be initiated. Penicillamine is commonly used at a dose of up to 1 g/day. [87] For patients unable to take oral medications, dimercaprol can be administered intramuscularly at a dose of 3 mg/kg body weight every 4 hours [88] until life-threatening symptoms subside. In cases of coagulopathy, [89] DMSA is recommended at a dose of 10 mg/kg body weight every 8 hours for 5 days, followed by every 12 hours for 2 weeks. [90] Kidney dialysis may also be considered. [91]

Preparations and form of the drug

Related Research Articles

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<span class="mw-page-title-main">Philadelphia chromosome</span> Genetic abnormality in leukemia cancer cells

The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells. This chromosome is defective and unusually short because of reciprocal translocation, t(9;22)(q34;q11), of genetic material between chromosome 9 and chromosome 22, and contains a fusion gene called BCR-ABL1. This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for a hybrid protein: a tyrosine kinase signaling protein that is "always on", causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle.

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<span class="mw-page-title-main">Acute promyelocytic leukemia</span> Subtype of acute myeloid leukaemia characterised by accumulation of promyelocytes

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2O
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<span class="mw-page-title-main">Bcl-2 family</span>

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<span class="mw-page-title-main">Paraptosis</span> Type of programmed cell death distinct from apoptosis and necrosis

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References

  1. 1 2 Modrzejewski, Feliks (1977). Farmacja stosowana, podręcznik dla studentów farmacji[Applied Pharmacy: A Textbook for Pharmacy Students] (in Polish). Vol. V. Warsaw: Państwowy Zakład Wydawnictw Lekarskich. p. 384.
  2. ↑ "FDA Grants Orphan Drug Designation To Trisenox (Arsenic Trioxide) For Treatment Of Chronic And Acute Myeloid Leukemia". pslgroup.com. Archived from the original on 2008-05-11.
  3. ↑ "Agency for Toxic Substances and Disease Registry. Arsenic". atsdr.cdc.gov. 2007. Archived from the original on 2001-12-16.
  4. 1 2 Aronson, S. M. (1994). "Arsenic and old myths". Rhode Island Medicine. 77 (7): 233–234. ISSN   1061-222X. PMID   7919541.
  5. ↑ Siderov, Jim; Duggan, John (2010). "Arsenic trioxide associated toothache". Journal of Oncology Pharmacy Practice. 16 (2): 127–128. doi:10.1177/1078155209338727. ISSN   1078-1552. PMID   19525303.
  6. ↑ Jinzhu, Wu (2008). Development and evaluation of a novel nanoparticulate delivery system of arsenic sulfides (a thesis submitted for the degree of doctor of philosophy, Department of Pharmacy, National University of Singapore) (PDF). p. 4.
  7. 1 2 Antman, Karen H. (1 April 2001). "Introduction: The History of Arsenic Trioxide in Cancer Therapy". The Oncologist. 6 (S2): 1–2. doi:10.1634/theoncologist.6-suppl_2-1. ISSN   1083-7159. PMID   11331433.
  8. ↑ Gensini, Gian Franco; Conti, Andrea Alberto; Lippi, Donatella (2007). "The contributions of Paul Ehrlich to infectious disease". Journal of Infection. 54 (3): 221–224. doi:10.1016/j.jinf.2004.05.022. PMID   16567000.
  9. ↑ Douer, Dan; Tallman, Martin S. (1 April 2005). "Arsenic Trioxide: New Clinical Experience With an Old Medication in Hematologic Malignancies". Journal of Clinical Oncology. 23 (10): 2396–2410. doi:10.1200/JCO.2005.10.217. ISSN   0732-183X. PMID   15800332.
  10. ↑ Waxman, Samuel; Anderson, Kenneth C. (1 April 2001). "History of the Development of Arsenic Derivatives in Cancer Therapy". The Oncologist. 6 (S2): 3–10. doi:10.1634/theoncologist.6-suppl_2-3. ISSN   1083-7159. PMID   11331434.
  11. ↑ Cutler, E. G.; Bradford, E. H. (10 January 1879). "Changes of the Globular Richness of Human Blood". The Journal of Physiology. 1 (6): 427–433. doi:10.1113/jphysiol.1879.sp000034. ISSN   0022-3751. PMC   1484689 . PMID   16991244.
  12. ↑ Forkner, Claude E.; Scott, T. (4 July 1931). "Arsenic as a therapeutic agent in chronic myelogenous leukemia". Journal of the American Medical Association. 97 (1): 3. doi:10.1001/jama.1931.02730010007002. ISSN   0002-9955.
  13. ↑ Shen, Z. X.; Chen, G. Q.; Ni, J. H.; Li, X. S.; Xiong, S. M.; Qiu, Q. Y.; Zhu, J.; Tang, W.; Sun, G. L.; Yang, K. Q.; Chen, Y.; Zhou, L.; Fang, Z. W.; Wang, Y. T.; Ma, J. (1 May 1997). "Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients". Blood. 89 (9): 3354–3360. doi:10.1182/blood.V89.9.3354. ISSN   0006-4971. PMID   9129042.
  14. ↑ Niu, C.; Yan, H.; Yu, T.; Sun, H. P.; Liu, J. X.; Li, X. S.; Wu, W.; Zhang, F. Q.; Chen, Y.; Zhou, L.; Li, J. M.; Zeng, X. Y.; Yang, R. R.; Yuan, M. M.; Ren, M. Y. (15 November 1999). "Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients". Blood. 94 (10): 3315–3324. doi:10.1182/blood.V94.10.3315.422k16_3315_3324. ISSN   0006-4971. PMID   10552940.
  15. ↑ Shen, Y; Shen, Z. X; Yan, H; Chen, J; Zeng, X. Y; Li, J. M; Li, X. S; Wu, W; Xiong, S. M; Zhao, W. L; Tang, W; Wu, F; Liu, Y. F; Niu, C; Wang, Z. Y (1 May 2001). "Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia: a comparison with conventional dosage". Leukemia. 15 (5): 735–741. doi:10.1038/sj.leu.2402106. ISSN   0887-6924. PMID   11368433.
  16. ↑ Soignet, Steven L.; Maslak, Peter; Wang, Zhu-Gang; Jhanwar, Suresh; Calleja, Elizabeth; Dardashti, Laura J.; Corso, Diane; DeBlasio, Anthony; Gabrilove, Janice; Scheinberg, David A.; Pandolfi, Pier Paolo; Warrell, Raymond P. (5 November 1998). "Complete Remission after Treatment of Acute Promyelocytic Leukemia with Arsenic Trioxide". New England Journal of Medicine. 339 (19): 1341–1348. doi:10.1056/NEJM199811053391901. ISSN   0028-4793. PMID   9801394.
  17. ↑ "FDA approves arsenic trioxide for leukemia treatment in record time for a cancer drug development program". labenz.org. 26 August 2000. Archived from the original on 2014-06-06.
  18. ↑ Petros, Andrew M.; Medek, Ales; Nettesheim, David G.; Kim, Daniel H.; Yoon, Ho Sup; Swift, Kerry; Matayoshi, Edmund D.; Oltersdorf, Tilman; Fesik, Stephen W. (13 March 2001). "Solution structure of the antiapoptotic protein bcl-2". Proceedings of the National Academy of Sciences. 98 (6): 3012–3017. Bibcode:2001PNAS...98.3012P. doi: 10.1073/pnas.041619798 . ISSN   0027-8424. PMC   30598 . PMID   11248023.
  19. ↑ Ye, Hong; Cande, Celine; Stephanou, Nicolas C.; Jiang, Sulin; Gurbuxani, Sundeep; Larochette, Nathanael; Daugas, Eric; Garrido, Carmen; Kroemer, Guido; Wu, Hao (2002). "DNA binding is required for the apoptogenic action of apoptosis inducing factor". Nature Structural Biology. 9 (9): 680–684. doi:10.1038/nsb836. PMID   12198487.
  20. ↑ Riedl, Stefan J.; Li, Wenyu; Chao, Yang; Schwarzenbacher, Robert; Shi, Yigong (2005). "Structure of the apoptotic protease-activating factor 1 bound to ADP". Nature. 434 (7035): 926–933. Bibcode:2005Natur.434..926R. doi:10.1038/nature03465. ISSN   0028-0836. PMID   15829969.
  21. ↑ Wang, H. (2008), Crystal structure of human Bcl-2 family protein Bak, doi:10.2210/pdb2yv6/pdb , retrieved 2024-09-26
  22. ↑ Suzuki, Motoshi; Youle, Richard J.; Tjandra, Nico (2000). "Structure of Bax". Cell. 103 (4): 645–654. doi:10.1016/S0092-8674(00)00167-7. PMID   11106734.
  23. ↑ Moorthy, Anu K.; Huang, De-Bin; Wang, Vivien Ya-Fan; Vu, Don; Ghosh, Gourisankar (2007). "X-ray Structure of a NF-κB p50/RelB/DNA Complex Reveals Assembly of Multiple Dimers on Tandem κB Sites". Journal of Molecular Biology. 373 (3): 723–734. doi:10.1016/j.jmb.2007.08.039. PMC   4167888 . PMID   17869269.
  24. ↑ Asano, Yasutomi; Kitamura, Shuji; Ohra, Taiichi; Aso, Kazuyoshi; Igata, Hideki; Tamura, Tomoko; Kawamoto, Tomohiro; Tanaka, Toshimasa; Sogabe, Satoshi; Matsumoto, Shin-ichi; Yamaguchi, Masashi; Kimura, Hiroyuki; Itoh, Fumio (2008). "Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1)". Bioorganic & Medicinal Chemistry. 16 (8): 4715–4732. doi:10.1016/j.bmc.2008.02.027. PMID   18313304.
  25. ↑ LeBlanc, H. N.; Ashkenazi, A. (2003). "Apo2L/TRAIL and its death and decoy receptors". Cell Death and Differentiation. 10 (1): 66–75. doi:10.1038/sj.cdd.4401187. ISSN   1350-9047. PMID   12655296.
  26. ↑ Łabedzka, Karolina; Grzanka, Alina; Izdebska, Magdalena (2006). "Mitochondria a śmierć komórki" [Mitochondria and cell death]. Postepy Higieny I Medycyny Doswiadczalnej (Online) (in Polish). 60: 439–446. ISSN   1732-2693. PMID   17013363.
  27. ↑ Bednarek, Jolanta; Kiliańska, Zofia M. (2005). "Mitochondrial intermembrane space proteins in apoptosis process". Postepy Biochemii. 51 (4): 447–458. ISSN   0032-5422. PMID   16676580.
  28. ↑ Pop, Cristina; Salvesen, Guy S. (14 August 2009). "Human caspases: activation, specificity, and regulation". The Journal of Biological Chemistry. 284 (33): 21777–21781. doi: 10.1074/jbc.R800084200 . ISSN   0021-9258. PMC   2755903 . PMID   19473994.
  29. ↑ Stepień, Aleksandra; Izdebska, Magdalena; Grzanka, Alina (9 July 2007). "Rodzaje śmierci komórki" [The types of cell death]. Postepy Higieny I Medycyny Doswiadczalnej (Online) (in Polish). 61: 420–428. ISSN   1732-2693. PMID   17679912.
  30. ↑ Jing, Yongkui (2004). "The PML-RARα Fusion Protein and Targeted Therapy for Acute Promyelocytic Leukemia". Leukemia & Lymphoma. 45 (4): 639–648. doi:10.1080/10428190310001609933. ISSN   1042-8194. PMID   15160934.
  31. ↑ Powell, Bayard L. (2001). "Acute progranulocytic leukemia". Current Opinion in Oncology. 13 (1): 8–13. doi:10.1097/00001622-200101000-00003. ISSN   1040-8746. PMID   11148679.
  32. ↑ Hayakawa, Fumihiko; Privalsky, Martin L (2004). "Phosphorylation of PML by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis". Cancer Cell. 5 (4): 389–401. doi:10.1016/S1535-6108(04)00082-0. PMID   15093545.
  33. ↑ Kang, Young-Hee; Lee, Su-Jae (2008). "The role of p38 MAPK and JNK in Arsenic trioxide-induced mitochondrial cell death in human cervical cancer cells". Journal of Cellular Physiology. 217 (1): 23–33. doi:10.1002/jcp.21470. ISSN   0021-9541. PMID   18412143.
  34. ↑ Davison, Kelly; Mann, Koren K.; Waxman, Samuel; Miller, Wilson H. (1 May 2004). "JNK activation is a mediator of arsenic trioxide-induced apoptosis in acute promyelocytic leukemia cells". Blood. 103 (9): 3496–3502. doi:10.1182/blood-2003-05-1412. ISSN   0006-4971. PMID   14701702.
  35. 1 2 3 Mathas, Stephan; Lietz, Andreas; Janz, Martin; Hinz, Michael; Jundt, Franziska; Scheidereit, Claus; Bommert, Kurt; Dörken, Bernd (1 August 2003). "Inhibition of NF-κB essentially contributes to arsenic-induced apoptosis". Blood. 102 (3): 1028–1034. doi: 10.1182/blood-2002-04-1154 . ISSN   0006-4971. PMID   12676792.
  36. ↑ Verma, U.; Yamamoto, Y.; Prajapati, S.; Gaynor, R. (2004). "Nuclear role of I kappa B Kinase-gamma/NF-kappa B essential modulator (IKK gamma/NEMO) in NF-kappa B-dependent gene expression". Journal of Biological Chemistry. 5 (279): 3509–3515. doi: 10.1074/jbc.M309300200 . PMID   14597638.
  37. ↑ Kerbauy, Daniella M. B.; Lesnikov, Vladimir; Abbasi, Nissa; Seal, Sudeshna; Scott, Bart; Deeg, H. Joachim (1 December 2005). "NF-kappaB and FLIP in arsenic trioxide (ATO)-induced apoptosis in myelodysplastic syndromes (MDSs)". Blood. 106 (12): 3917–3925. doi:10.1182/blood-2005-04-1424. ISSN   0006-4971. PMC   1895102 . PMID   16105982.
  38. ↑ Miller, Wilson H.; Schipper, Hyman M.; Lee, Janet S.; Singer, Jack; Waxman, Samuel (15 July 2002). "Mechanisms of action of arsenic trioxide". Cancer Research. 62 (14): 3893–3903. ISSN   0008-5472. PMID   12124315.
  39. ↑ Ai, Zhilong; Lu, Weiqi; Qin, Xinyu (2006). "Arsenic trioxide induces gallbladder carcinoma cell apoptosis via downregulation of Bcl-2". Biochemical and Biophysical Research Communications. 348 (3): 1075–1081. doi:10.1016/j.bbrc.2006.07.181. PMID   16904648.
  40. ↑ Chen, G. Q.; Zhu, J.; Shi, X. G.; Ni, J. H.; Zhong, H. J.; Si, G. Y.; Jin, X. L.; Tang, W.; Li, X. S.; Xong, S. M.; Shen, Z. X.; Sun, G. L.; Ma, J.; Zhang, P.; Zhang, T. D. (1 August 1996). "In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins". Blood. 88 (3): 1052–1061. doi:10.1182/blood.V88.3.1052.1052. ISSN   0006-4971. PMID   8704214.
  41. ↑ Freitas, Rosana Aparecida; Silva dos Santos, Guilherme Augusto; Gimenes Teixeira, Hamilton Luiz; Scheucher, Priscila Santos; Lucena-Araujo, Antonio Roberto; Lima, Ana Sílvia Gouveia; Abreu e Lima, Rodrigo Siqueira; Garcia, Aglair Bergamo; Jordão, Alceu Afonso; Falcão, Roberto Passetto; Vannucchi, Hélio; Rego, Eduardo Magalhães (2009). "Apoptosis induction by (+)α-tocopheryl succinate in the absence or presence of all-trans retinoic acid and arsenic trioxide in NB4, NB4-R2 and primary APL cells". Leukemia Research. 33 (7): 958–963. doi:10.1016/j.leukres.2008.09.035. PMID   19013639.
  42. ↑ Kitamura, K.; Minami, Y.; Yamamoto, K.; Akao, Y.; Kiyoi, H.; Saito, H.; Naoe, T. (2000). "Involvement of CD95-independent caspase 8 activation in arsenic trioxide-induced apoptosis". Leukemia. 14 (10): 1743–1750. doi:10.1038/sj.leu.2401900. ISSN   0887-6924. PMID   11021749.
  43. ↑ Zhu, Jiebin; Okumura, Hirokazu; Ohtake, Shigeki; Nakamura, Shinobu; Nakao, Shinji (2003). "Arsenic trioxide induces apoptosis in leukemia/lymphoma cell lines via the CD95/CD95L system". Oncology Reports. 10 (3): 705–709. ISSN   1021-335X. PMID   12684647.
  44. 1 2 Liu, Qun; Hilsenbeck, Susan; Gazitt, Yair (15 May 2003). "Arsenic trioxide–induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL". Blood. 101 (10): 4078–4087. doi:10.1182/blood-2002-10-3231. ISSN   1528-0020. PMID   12531793.
  45. ↑ Szegezdi, E; Cahill, S; Meyer, M; O'Dwyer, M; Samali, A (2006). "TRAIL sensitisation by arsenic trioxide is caspase-8 dependent and involves modulation of death receptor components and Akt". British Journal of Cancer. 94 (3): 398–406. doi:10.1038/sj.bjc.6602954. ISSN   0007-0920. PMC   2361137 . PMID   16434995.
  46. ↑ Coe, Emma; Schimmer, Aaron D. (2008). "Catalase activity and arsenic sensitivity in acute leukemia". Leukemia & Lymphoma. 49 (10): 1976–1981. doi:10.1080/10428190802353617. ISSN   1042-8194. PMID   18949620.
  47. ↑ Cheng, Ya-Hsin; Ou, Bor-Rung; Cheng, Li-Chuan; Lu, Jian-He; Yeh, Jan-Ying (2008). "Glutathione regulation in arsenic-induced porcine aortic endothelial cells". Toxicology in Vitro. 22 (8): 1832–1839. Bibcode:2008ToxVi..22.1832C. doi:10.1016/j.tiv.2008.08.006. PMID   18801422.
  48. ↑ Bilska, Anna; Kryczyk, Agata; Włodek, Lidia (11 July 2007). "Różne oblicza biologicznej roli glutationu" [The different aspects of the biological role of glutathione]. Postepy Higieny I Medycyny Doswiadczalnej (Online) (in Polish). 61: 438–453. ISSN   1732-2693. PMID   17679914.
  49. ↑ Ishitsuka, Kenji; Ikeda, Ryuji; Utsunomiya, Atae; Uozumi, Kimiharu; Hanada, Shuichi; Suzuki, Shinsuke; Takeuchi, Shogo; Takatsuka, Yoshifusa; Takeshita, Taketsugu; Ohno, Nobuhito; Arima, Terukatsu (2002). "Arsenic trioxide induces apoptosis in HTLV-I infected T-cell lines and fresh adult T-cell leukemia cells through CD95 or tumor necrosis factor alpha receptor independent caspase activation". Leukemia & Lymphoma. 43 (5): 1107–1114. doi:10.1080/10428190290021461. ISSN   1042-8194. PMID   12148893.
  50. ↑ Zhao, Shiguang; Zhang, Jian; Zhang, Xu; Dong, Xuesong; Sun, Xueying (2008). "Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status". Molecular Biology Reports. 35 (3): 421–429. doi:10.1007/s11033-007-9102-6. ISSN   0301-4851. PMID   17530438.
  51. ↑ Izdebska, Magdalena; Grzanka, Alina; Szczepański, Mariusz Andrzej; Litwiniec, Anna (9 September 2008). "Wybrane mechanizmy terapeutycznego oddziaływania trójtlenku arsenu w leczeniu nowotworów" [Selected mechanisms of the therapeutic effect of arsenic trioxide in cancer treatment]. Postepy Higieny I Medycyny Doswiadczalnej (Online) (in Polish). 62: 463–467. ISSN   1732-2693. PMID   18806735.
  52. ↑ Hussein, Mohamad A.; Saleh, Mansoor; Ravandi, Farhad; Mason, James; Rifkin, Robert M.; Ellison, Ralph (2004). "Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma". British Journal of Haematology. 125 (4): 470–476. doi:10.1111/j.1365-2141.2004.04941.x. ISSN   0007-1048. PMID   15142117.
  53. ↑ Soignet, S. L.; Frankel, S. R.; Douer, D.; Tallman, M. S.; Kantarjian, H.; Calleja, E.; Stone, R. M.; Kalaycio, M.; Scheinberg, D. A.; Steinherz, P.; Sievers, E. L.; Coutré, S.; Dahlberg, S.; Ellison, R.; Warrell, R. P. (15 September 2001). "United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia". Journal of Clinical Oncology. 19 (18): 3852–3860. doi:10.1200/JCO.2001.19.18.3852. ISSN   0732-183X. PMID   11559723.
  54. ↑ Fox, Elizabeth; Razzouk, Bassem I.; Widemann, Brigitte C.; Xiao, Shaun; O'Brien, Michelle; Goodspeed, Wendy; Reaman, Gregory H.; Blaney, Susan M.; Murgo, Anthony J.; Balis, Frank M.; Adamson, Peter C. (15 January 2008). "Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma". Blood. 111 (2): 566–573. doi:10.1182/blood-2007-08-107839. ISSN   0006-4971. PMC   2200837 . PMID   17959855.
  55. ↑ Kim, Hak-Ryul; Kim, Eun-Jung; Yang, Sei-Hoon; Jeong, Eun-Taik; Park, Channy; Kim, Se-Jin; Youn, Myung-Ja; So, Hong-Seob; Park, Raekil (2006). "Combination treatment with arsenic trioxide and sulindac augments their apoptotic potential in lung cancer cells through activation of caspase cascade and mitochondrial dysfunction". International Journal of Oncology. 28 (6): 1401–1408. ISSN   1019-6439. PMID   16685442.
  56. ↑ Qazilbash, Muzaffar H.; Saliba, Rima M.; Nieto, Yago; Parikh, Gaurav; Pelosini, Matteo; Khan, Fatima B.; Jones, Roy B.; Hosing, Chitra; Mendoza, Floralyn; Weber, Donna M.; Wang, Michael; Popat, Uday; Alousi, Amin; Anderlini, Paolo; Champlin, Richard E. (2008). "Arsenic trioxide with ascorbic acid and high-dose melphalan: results of a phase II randomized trial". Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation. 14 (12): 1401–1407. doi:10.1016/j.bbmt.2008.09.019. ISSN   1523-6536. PMC   4112362 . PMID   19041063.
  57. ↑ Campbell, Richard A.; Sanchez, Eric; Steinberg, Jeffrey A.; Baritaki, Stavroula; Gordon, Melinda; Wang, Cathy; Shalitin, Dror; Chen, Haiming; Pang, Shen; Bonavida, Benjamin; Said, Jonathan; Berenson, James R. (2007). "Antimyeloma effects of arsenic trioxide are enhanced by melphalan, bortezomib and ascorbic acid". British Journal of Haematology. 138 (4): 467–478. doi:10.1111/j.1365-2141.2007.06675.x. ISSN   0007-1048. PMID   17587338.
  58. ↑ Bornstein, Jacob; Sagi, Shlomi; Haj, Amer; Harroch, Jeffrey; Fares, Fuad (2005). "Arsenic Trioxide inhibits the growth of human ovarian carcinoma cell line". Gynecologic Oncology. 99 (3): 726–729. doi:10.1016/j.ygyno.2005.07.125. ISSN   0090-8258. PMID   16243384.
  59. ↑ Shao, Qin-Shu; Ye, Zai-Yuan; Ling, Zhi-Qiang; Ke, Jin-Jing (14 June 2005). "Cell cycle arrest and apoptotic cell death in cultured human gastric carcinoma cells mediated by arsenic trioxide". World Journal of Gastroenterology. 11 (22): 3451–3456. doi: 10.3748/wjg.v11.i22.3451 . ISSN   1007-9327. PMC   4316002 . PMID   15948253.
  60. ↑ Uslu, R.; Sanli, U. A.; Sezgin, C.; Karabulut, B.; Terzioglu, E.; Omay, S. B.; Goker, E. (2000). "Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines". Clinical Cancer Research. 6 (12): 4957–4964. ISSN   1078-0432. PMID   11156257.
  61. ↑ Zhao, Shiguang; Zhang, Xu; Zhang, Jian; Zhang, Jianhua; Zou, Huichao; Liu, Yaohua; Dong, Xuesong; Sun, Xueying (2008). "Intravenous administration of arsenic trioxide encapsulated in liposomes inhibits the growth of C6 gliomas in rat brains". Journal of Chemotherapy (Florence, Italy). 20 (2): 253–262. doi:10.1179/joc.2008.20.2.253. ISSN   1973-9478. PMID   18467254.
  62. ↑ Wang, Wei; Adachi, Masaaki; Zhang, Rong; Zhou, Jin; Zhu, Daling (2009). "A novel combination therapy with arsenic trioxide and parthenolide against pancreatic cancer cells". Pancreas. 38 (4): e114–123. doi:10.1097/MPA.0b013e3181a0b6f2. ISSN   1536-4828. PMID   19342982.
  63. ↑ Chen, Haimei; Ahn, Richard; Van den Bossche, Jeroen; Thompson, David H.; O'Halloran, Thomas V. (2009). "Folate-mediated intracellular drug delivery increases the anticancer efficacy of nanoparticulate formulation of arsenic trioxide". Molecular Cancer Therapeutics. 8 (7): 1955–1963. doi:10.1158/1535-7163.MCT-09-0045. ISSN   1538-8514. PMC   3098497 . PMID   19567824.
  64. ↑ Bobé, Pierre; Bonardelle, Danielle; Benihoud, Karim; Opolon, Paule; Chelbi-Alix, Mounira K. (15 December 2006). "Arsenic trioxide: A promising novel therapeutic agent for lymphoproliferative and autoimmune syndromes in MRL/lpr mice". Blood. 108 (13): 3967–3975. doi:10.1182/blood-2006-04-020610. ISSN   0006-4971. PMID   16926289.
  65. 1 2 3 "Arsenic Trioxide Monograph for Professionals". Drugs.com. Retrieved 2024-09-27.
  66. ↑ Yoshino, Yuta; Yuan, Bo; Miyashita, Shin-ich; Iriyama, Noriyoshi; Horikoshi, Akira; Shikino, Osamu; Toyoda, Hiroo; Kaise, Toshikazu (2009). "Speciation of arsenic trioxide metabolites in blood cells and plasma of a patient with acute promyelocytic leukemia". Analytical and Bioanalytical Chemistry. 393 (2): 689–697. doi:10.1007/s00216-008-2487-9. ISSN   1618-2650. PMID   19009285.
  67. ↑ Carter, Dean E.; Aposhian, H. Vasken; Gandolfi, A. Jay (15 December 2003). "The metabolism of inorganic arsenic oxides, gallium arsenide, and arsine: a toxicochemical review". Toxicology and Applied Pharmacology. 193 (3): 309–334. Bibcode:2003ToxAP.193..309C. doi:10.1016/j.taap.2003.07.009. ISSN   0041-008X. PMID   14678742.
  68. ↑ Ni, J.; Chen, G.; Shen, Z.; Li, X.; Liu, H.; Huang, Y.; Fang, Z.; Chen, S.; Wang, Z.; Chen, Z. (1998). "Pharmacokinetics of intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia". Chinese Medical Journal. 111 (12): 1107–1110. ISSN   0366-6999. PMID   11263375.
  69. ↑ Fujisawa, Shinya; Ohno, Ryuzo; Shigeno, Kazuyuki; Sahara, Naohi; Nakamura, Satoki; Naito, Kensuke; Kobayashi, Miki; Shinjo, Kaori; Takeshita, Akihiro; Suzuki, Yoshinari; Hashimoto, Hisakuni; Kinoshita, Kenji; Shimoya, Masahito; Kaise, Toshikazu; Ohnishi, Kazunori (2007). "Pharmacokinetics of arsenic species in Japanese patients with relapsed or refractory acute promyelocytic leukemia treated with arsenic trioxide". Cancer Chemotherapy and Pharmacology. 59 (4): 485–493. doi:10.1007/s00280-006-0288-4. ISSN   0344-5704. PMID   16937107.
  70. ↑ Thomas, Xavier; Pigneux, Arnaud; Raffoux, Emmanuel; Huguet, Francoise; Caillot, Denis; Fenaux, Pierre (2006). "Superiority of an arsenic trioxide-based regimen over a historic control combining all-trans retinoic acid plus intensive chemotherapy in the treatment of relapsed acute promyelocytic leukemia". Haematologica. 91 (7): 996–997. ISSN   1592-8721. PMID   16757416.
  71. 1 2 3 4 Au, Wing-Yan; Kwong, Yok-Lam (2008). "Arsenic trioxide: safety issues and their management". Acta Pharmacologica Sinica. 29 (3): 296–304. doi:10.1111/j.1745-7254.2008.00771.x. ISSN   1745-7254. PMID   18298894.
  72. ↑ Abou-Jawde, Rony M.; Reed, Janice; Kelly, Megan; Walker, Esteban; Andresen, Steven; Baz, Rachid; Karam, Mary Ann; Hussein, Mohamad (2006). "Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients: a phase 2 trial". Medical Oncology (Northwood, London, England). 23 (2): 263–272. doi:10.1385/MO:23:2:263. ISSN   1357-0560. PMID   16720927.
  73. ↑ Vizzardi, Enrico; Zanini, Gregoriana; Antonioli, Elena; D'Aloia, Antonio; Raddino, Riccardo; Cas, Livio Dei (2008). "QT prolongation: a case of arsenical pericardial and pleural effusion". Cardiovascular Toxicology. 8 (1): 41–44. doi:10.1007/s12012-007-9009-4. ISSN   1559-0259. PMID   18084726.
  74. ↑ Naito, Kensuke; Kobayashi, Miki; Sahara, Naohi; Shigeno, Kazuyuki; Nakamura, Satoki; Shinjo, Kaori; Tobita, Tadasu; Takeshita, Akihiro; Ohno, Ryuzo; Ohnishi, Kazunori (2006). "Two cases of acute promyelocytic leukemia complicated by torsade de pointes during arsenic trioxide therapy". International Journal of Hematology. 83 (4): 318–323. doi:10.1532/IJH97.05056. ISSN   0925-5710. PMID   16757431.
  75. ↑ Chanan-Khan, Asher; Srinivasan, Sridhar; Czuczman, Myron S. (2004). "Prevention and management of cardiotoxicity from antineoplastic therapy". The Journal of Supportive Oncology. 2 (3): 251–256, discussion 259–261, 264–266. ISSN   1544-6794. PMID   15328825.
  76. ↑ Unnikrishnan, D.; Dutcher, J. P.; Garl, S.; Varshneya, N.; Lucariello, R.; Wiernik, P. H. (2004). "Cardiac monitoring of patients receiving arsenic trioxide therapy". British Journal of Haematology. 5 (124): 610–617. doi:10.1111/j.1365-2141.2003.04817.x. PMID   14871247.
  77. ↑ Ohnishi, K.; Yoshida, H.; Shigeno, K.; Nakamura, S.; Fujisawa, S.; Naito, K.; Shinjo, K.; Fujita, Y.; Matsui, H.; Sahara, N.; Takeshita, A.; Satoh, H.; Terada, H.; Ohno, R. (2002). "Arsenic trioxide therapy for relapsed or refractory Japanese patients with acute promyelocytic leukemia: need for careful electrocardiogram monitoring". Leukemia. 16 (4): 617–622. doi:10.1038/sj.leu.2402426. ISSN   0887-6924. PMID   11960341.
  78. ↑ Cashin, Richard; Burry, Lisa; Peckham, Kenneth; Reynolds, Stuart; Seki, Jack T. (15 May 2008). "Acute renal failure, gastrointestinal bleeding, and cardiac arrhythmia after administration of arsenic trioxide for acute promyelocytic leukemia". American Journal of Health-System Pharmacy. 65 (10): 941–946. doi:10.2146/ajhp060616. ISSN   1535-2900. PMID   18463343.
  79. 1 2 Yamazaki, Keisuke; Terada, Hajime; Satoh, Hiroshi; Naito, Kensuke; Takeshita, Akihiro; Uehara, Akihiko; Katoh, Hideki; Ohnishi, Kazunori; Hayashi, Hideharu (2006). "Arrhythmogenic effects of arsenic trioxide in patients with acute promyelocytic leukemia and an electrophysiological study in isolated guinea pig papillary muscles". Circulation Journal. 70 (11): 1407–1414. doi:10.1253/circj.70.1407. hdl: 10271/361 . ISSN   1346-9843. PMID   17062962.
  80. 1 2 Jones, Robin L.; Ewer, Michael S. (2006). "Cardiac and cardiovascular toxicity of nonanthracycline anticancer drugs". Expert Review of Anticancer Therapy. 6 (9): 1249–1269. doi:10.1586/14737140.6.9.1249. ISSN   1744-8328. PMID   17020459.
  81. 1 2 Rust, D. M.; Soignet, S. L. (2001). "Risk/benefit profile of arsenic trioxide". The Oncologist. 6 Suppl 2: 29–32. doi:10.1634/theoncologist.6-suppl_2-29. ISSN   1083-7159. PMID   11331438.
  82. ↑ Levy, Michael; Wofford, Marcia M.; Powell, Bayard L.; McLean, Thomas W. (2008). "Hyperleukocytosis from arsenic trioxide". Pediatric Blood & Cancer. 50 (6): 1265–1267. doi:10.1002/pbc.21532. ISSN   1545-5017. PMID   18300308.
  83. ↑ Roberts, T. F.; Sprague, K.; Schenkein, D.; Miller, K. B.; Relias, V. (1 December 2000). "Hyperleukocytosis during induction therapy with arsenic trioxide for relapsed acute promyelocytic leukemia associated with central nervous system infarction". Blood. 96 (12): 4000–4001. doi:10.1182/blood.V96.12.4000. ISSN   0006-4971. PMID   11186272.
  84. ↑ Thery, Jean-Christophe; Jardin, Fabrice; Massy, Nathalie; Massy, Jerome; Stamatoullas, Aspasia; Tilly, Hervé (2008). "Optical neuropathy possibly related to arsenic during acute promyelocytic leukemia treatment". Leukemia & Lymphoma. 49 (1): 168–170. doi:10.1080/10428190701757843. ISSN   1029-2403. PMID   18203030.
  85. ↑ Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Jahani, Mohamad (2006). "Use of Novoseven for arsenic trioxide-induced bleeding in PML". American Journal of Hematology. 81 (9): 720. doi:10.1002/ajh.20713. ISSN   0361-8609. PMID   16804937.
  86. 1 2 "Trisenox Uses, Side Effects & Warnings". Drugs.com. Retrieved 2024-09-27.
  87. ↑ Wang, Ernest E.; Mahajan, Niraj; Wills, Brandon; Leikin, Jerrold (2007). "Successful treatment of potentially fatal heavy metal poisonings". The Journal of Emergency Medicine. 32 (3): 289–294. doi:10.1016/j.jemermed.2006.12.013. ISSN   0736-4679. PMID   17394994.
  88. ↑ Kim, Lawrence H. C.; Abel, Simon J. C. (2009). "Survival after a massive overdose of arsenic trioxide". Critical Care and Resuscitation: Journal of the Australasian Academy of Critical Care Medicine. 11 (1): 42–45. doi: 10.1016/S1441-2772(23)01832-X . ISSN   1441-2772. PMID   19281444.
  89. ↑ Korístek, Z.; Zák, P. (2008). "[Coagulopathy and differentiation syndrome: the main complications of the initial treatment of acute promyelocytic leukemia]". Vnitrni Lekarstvi. 54 (7–8): 745–750. ISSN   0042-773X. PMID   18780573.
  90. ↑ Kreppel, H.; Paepcke, U.; Thiermann, H.; Szinicz, L.; Reichl, F. X.; Singh, P. K.; Jones, M. M. (1993). "Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute arsenic trioxide poisoning in mice". Archives of Toxicology. 67 (8): 580–585. Bibcode:1993ArTox..67..580K. doi:10.1007/BF01969272. ISSN   0340-5761. PMID   7506906.
  91. ↑ Blythe, D.; Joyce, D. A. (2001). "Clearance of arsenic by haemodialysis after acute poisoning with arsenic trioxide". Intensive Care Medicine. 27 (1): 334. doi:10.1007/s001340000770. ISSN   0342-4642. PMID   11280669.
  92. 1 2 3 4 "Trisenox (Arsenic Trioxide Injection): Side Effects, Uses, Dosage, Interactions, Warnings". RxList. Retrieved 2024-09-27.
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