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Systematic Review of Intravenous Ascorbate in Cancer Clinical Trials.

BackgroundAscorbate (vitamin C) has been evaluated as a potential treatment for cancer as an independent agent and in combination with standard chemotherapies. This review assesses the evidence for safety and clinical effectiveness of intravenous (IV) ascorbate in treating various types of cancer.MethodsSingle arm and randomized Phase I/II trials were included in this review. The PubMed, MEDLINE, and Cochrane databases were searched. Results were screened by three of the authors (GN, RP, and CJP) to determine if they met inclusion criteria, and then summarized using a narrative approach.Result

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… Trials Evaluating Low-Dose Intravenous Ascorbic Acid in Combination with Arsenic Trioxide Out of the 23 clinical trials included in this paper, 11 trials with a total of 200 patients used low dose intravenous ascorbic acid in combination with arsenic trioxide (As 2 O 3 ) ( Table 1 ). … Phase II study of arsenic trioxide and ascorbic acid for relapsed or refractory lymphoid malignancies: A Wisconsin Oncology Network study Hematol. Oncol. 2009 27 11 16 10.1002/hon.870 18668698 PMC2897137 56. Bael T.E. Peterson B.L. Gollob J.A. …

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-in

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… Arsenic trioxide induces apoptosis through JNK and ERK in human mesothelioma cells. J Cell Physiol 2011; 226: 762–768. 62. Lam SK, Li YY, Zheng CY, et al. Downregulation of thymidylate synthase and E2F1 by arsenic trioxide in mesothelioma. Int J Oncol 2015; 46: 113–122. 63. … VEGFA expression is inhibited by arsenic trioxide in HUVECs through the upregulation of Ets-2 and miRNA-126. PLoS One 2015; 10: e0135795. 115. Wang H, Liu Y, Wang X, et al. …

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome.

The recent outbreak of Covid19 has required urgent treatments for numerous patients. No suitable vaccines or antivirals are available for Covid19. The efficiency against Covid19 of WHO therapies of choice, that are two antivirals developed for other pathologies, is controversial. Therefore, alternative approaches are required. Intravenous (IV) Vitamin C (Vit-C) has emerged as one of the other alternatives for this purpose. Here we review the effects of IV Vit-C on the immune system response, the antiviral properties of IV Vit-C, and finally the antioxidant properties of IV Vit-C to specificall

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… Several studies were performed small doses of IV ascorbic acid treatment (1000 mg) with arsenic trioxide regimens, and mixed results were obtained [ [68] , [69] , [70] ]. Clinical investigations of ascorbate in combination with arsenic trioxide were reported [ 36 ]. … Numerous studies used IV ascorbic acid at a fixed dose of 1000 mg with various amounts of arsenic trioxide as anticancer therapy. …

Oxidative Stress and Cancer: Harnessing the Therapeutic Potential of Curcumin and Analogues Against Cancer.

Reactive oxygen species (ROS) are a class of bioactive molecules that are the by-products of many cellular functions. These molecules are present in normal cells at homeostatic levels but have been studied extensively in cancer due to their dysregulation resulting in pro- and anti-tumorigenic environments. Completely understanding the paradoxical nature of ROS in cancer is imperative to fully realize its modulation as cancer therapy. Studies into ROS have shown far-reaching effects in cancer, including how ROS levels regulate signaling, response to treatment, drug resistance, etc. Many drugs w

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… Arsenic Trioxide is an interesting anti-cancer candidate that was tested with a variety of cancers for its ability to affect cancer stem-like cells, induce cell cycle arrest and apoptosis, chemo-sensitize, and decrease angiogenic potential. 41 Many clinical trials involving arsenic trioxide were undertaken … Acandidate for lung cancer treatment: arsenic trioxide . Clin Transl Oncol . 2019 ; 21 ( 9 ): 1115 – 1126 . 30756240 10.1007/s12094-019-02054-6 34. …

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms

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… trioxide-mediated apoptosis using docosahexaenoic acid in arsenic trioxide-resistant solid tumor cells International Journal of Cancer 2004 112 707 12 15382055 10.1002/ijc.20462 14 Sturlan S Baumgartner M Roth E Bachleitner-Hofmann T Docosahexaenoic acid enhances arsenic trioxide-mediated apoptosis … in arsenic trioxide-resistant HL-60 cells Blood 2003 101 4990 7 12609832 10.1182/blood-2002-08-2391 15 Fan YY McMurray DN Ly LH Chapkin RS Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts The Journal of nutrition 2003 133 1913 20 12771339 10.1093/jn/133.6.1913 16 Stulnig …

Полнотрансформатная ретиноидальная кислота в гематологическое расстройство: не только острая промиелоцитическая лейкемия.

Всетранс-ретиноиновая кислота (ATRA) играет определенную роль в развитии тканей, нейронной функции, воспроизводстве, зрение, росте и дифференциации клеток, иммунитете от опухоли и апоптозе. АТРА может действовать, вызывая автофагическую сигнализацию, ангиогенез, клеточную дифференциацию, апоптоз и иммунную функцию. В крови ATRA впервые с большим успехом использовалась в острой промиелоцитической лейкемии (APL), где ATRA дифференцировала клетки лейкемии на зрелые гранулоциты. АТРА может играть определенную роль не только в ППН, но и в других гематоологических заболеваниях, таких, как иммунная т

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… The combination of ATRA and arsenic trioxide has changed the treatment strategy for APL, making it an acute leukemia that can be cured without chemotherapy regimens ( Wang HY. et al., 2022 ; Kutny et al., 2022 ). … Arsenic trioxide (ATO, As2O3), a chemical derived from the ancient Chinese poison arsenic, was identified in the 1990s for the treatment of APL. …

As4S4 Exhibits Good Killing Effect on Multiple Myeloma Cells Via Repressing SOCS1 Methylation-Mediated JAK2/STAT3 Signaling Pathway.

ObjectiveThis study aimed to investigate the effect of tetra-arsenic tetra-sulfide on treating multiple myeloma and its potential regulation on suppressor of cytokine signaling 1 methylation-mediated Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway.MethodsTetra-arsenic tetra-sulfide with different concentrations were used to treat U266 cells, and cell viability was measured at 12, 24, and 48 hours with 0 μM tetra-arsenic tetra-sulfide treatment as control by Cell Counting Kit-8 assay. Suppressor of cytokine signaling 1 methylation and expression were determin

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… Tetraarsenictetrasulfide and arsenic trioxide exert synergistic effects on induction of apoptosis and differentiation in acute promyelocytic leukemia cells. PLoS One. 2015;10(6):e0130343. 10. Yin T, Wu YL, Sun HP, et al. … Arsenic trioxide induces SOCS-1 gene demethylation in myeloma cell lines [in Chinese]. Zhongguo shi yan xue ye xue za zhi. 2008;16(5):1064–1068. 16. Liu L, Tan L, He Z. …

Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.

The thioredoxin (Trx) system, an integral component of cellular redox regulation, preserves protein dithiol-disulfide equilibrium through its conserved Cys-Gly-Pro-Cys active site and is involved in key cellular functions, including cell proliferation, apoptosis, and signal transduction. In cancer biology, the thioredoxin system plays dual roles: overexpression can suppress oxidative stress and promote tumor growth, whereas dysfunction can trigger programmed cell death (PCD). However, a critical area for future research is to delineate how Trx modulates the intricate networks of PCD, and to id

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… - • Arsenic Trioxide With MAPK Inhibitors and Chemotherapy for Stage 4/M Neuroblastoma NCT06933394 Neuroblastoma RECRUITING 2025.05- • Fuzuloparib Arsenic Trioxide Platinum Resistance Relapsed Ovarian Cancer NCT04518501 Efficacy and Safety RECRUITING 2020.07- • Tretinoin and Arsenic Trioxide With or … Mutations | RECRUITING | 2023.12- • Oral-ATO for TP53-mutated Myeloid Malignancies | NCT06778187 | Acute Myeloid Leukemia, Myelodysplastic Neoplasm, Chronic Myelomonocytic Leukemia, TP53 Gene Mutation, Arsenic Trioxide | RECRUITING | 2025.02- • Frontline Oral Arsenic Trioxide for APL | NCT04687176 | …

Integrative Hematology: State of the Art.

Blood cancers are a group of diseases with thus far frequently poor prognosis. Although many new drugs, including target therapies, have been developed in recent years, there is still a need to expand our therapeutic armamentarium to better deal with these diseases. Integrative hematology was conceived as a discipline that enriches the patient's therapeutic possibilities with the use of supplements, vitamins and a nutritional approach aiming at improving the response to therapies and the clinical outcome. We will analyze the substances that have proved most useful in preclinical and clinical s

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… It also reduces the cardiotoxicity of arsenic trioxide, a drug used in acute promyelocytic leukemia, showing promise for its use in this patient setting [ 60 ]. … It accentuates the cytotoxicity mediated by arsenic trioxide, generating a dramatic increase in ROS compared to cells treated with arsenic trioxide alone, and reduces the intracellular GSH content [ 63 ]. 3. Lymphoid Malignancies 3.1. …

Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors.

The sonic hedgehog (Shh) signaling pathway is a major regulator of cell differentiation, cell proliferation, and tissue polarity. Aberrant activation of the Shh pathway has been shown in a variety of human cancers, including, basal cell carcinoma, malignant gliomas, medulloblastoma, leukemias, and cancers of the breast, lung, pancreas, and prostate. Tumorigenesis, tumor progression and therapeutic response have all been shown to be impacted by the Shh signaling pathway. Downstream effectors of the Shh pathway include smoothened (SMO) and glioma-associated oncogene homolog (GLI) family of zinc

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… Arsenic Trioxide (ATO) Arsenic trioxide is an FDA-approved inhibitor of GLI1 and GLI2 transcription factors. It has been approved for treatment of acute promyelocytic leukemia [ 119 ]. … Arsenic trioxide inhibits viability of pancreatic cancer stem cells in culture and in a xenograft model via binding to SHH-GLI OncoTargets Ther. 2013 6 1129 1138 10.2147/OTT.S49148 23990729 PMC3753152 129. Buglino J.A. Resh M.D. …

Therapies and nanotherapies for cervical cancer (Review).

Cervical cancer (CC) is a major global health concern, ranking fourth worldwide in mortality, due to its high death rate and strong link to persistent high-risk human papillomavirus infections, which drive cancer progression through cellular dysregulation. Conventional therapies used in the treatment of CC have significant disadvantages, such as adverse side effects that affect the quality of life of patients. These side effects may include nausea, vomiting, fatigue, hair loss, fertility problems, damage to nearby organs and systemic toxicity. To address these challenges, there has been an inc

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… For instance, the optimization of arsenic trioxide encapsulated in folate-mediated liposomes has demonstrated enhanced efficacy in the in vitro treatment of HPV-positive CC cells. … Optimisation of folate-mediated liposomal encapsulated arsenic trioxide for treating HPV-positive cervical cancer cells in vitro. Int J Mol Sci. 2019;20(2156) doi: 10.3390/ijms20092156. 49. You L, Liu X, Fang Z, Xu Q, Zhang Q. …

Integrating Nature Into Oncology: Enhancing Hematological Malignancies Therapies With Natural Medicine.

Hematological malignancies are complex clonal disorders that pose a significant threat to human health. Current treatment modalities, including radiotherapy, chemotherapy, immunotherapy, and bone marrow transplantation, have demonstrated efficacy but are often limited by side effects, drug resistance, and suboptimal cure rates. Natural medicines, as key elements of complementary and alternative medicine, exhibit considerable potential in combating hematological cancers. Particularly when used in combination with conventional therapies, they can enhance treatment efficacy and reverse drug resis

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… In recent years, arsenic trioxide has gained attention as a therapeutic agent for AML. Using network pharmacology approaches, Zeng et al. identified potential synergistic targets to arsenic trioxide and curcumin in AML, including TP53, MAPK3, MAPK1, STAT3, and SRC, and verified them experimentally. … These results underscore the potential of curcumin and arsenic trioxide as combined treatment strategies for AML, warranting further investigation and validation [ 10 ]. …

A Review of New Findings in Adult T-cell Leukemia-Lymphoma: A Focus on Current and Emerging Treatment Strategies.

Adult T-cell leukemia-lymphoma (ATL), a rare and aggressive T-cell malignancy caused by human T-cell lymphotropic virus type 1 (HTLV-1), is associated with a poor prognosis. Evidence-based standard treatment options are lacking and outcomes are generally unsatisfactory, particularly for patients with relapsed or refractory disease. Continued research is contributing to changing treatment landscape as a number of existing and investigational agents are evaluated. We describe the epidemiology of HTLV-1 and ATL, discuss the biology behind the disease, review current treatment practices and guidel

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… Hermine O Dombret H Poupon J Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma Hematol J 2004 5 130 134 10.1038/sj.thj.6200374 15048063 46. … Kchour G Tarhini M Kooshyar MM Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL) Blood 2009 113 6528 6532 10.1182/blood-2009-03-211821 19411628 88. …

The Dynamic Endothelial Activation and Stress Index (EASIX) as a Predictor of Early Death and Long-Term Survival in Acute Promyelocytic Leukemia (APL): A Multicenter Study.

Background/Objectives: Early death (ED) remains the primary barrier to long-term survival in acute promyelocytic leukemia (APL). Since current risk stratification models rely solely on static baseline parameters, they fail to capture the high biological volatility during the induction phase. We aimed to evaluate the prognostic value of the dynamic evolution of the endothelial activation and stress index (EASIX). Materials and Methods: This multicenter, retrospective study analyzed 131 newly diagnosed adult APL patients treated with the AIDA protocol. EASIX scores were calculated at admission (

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… Historically considered the most fatal AML subtype due to severe coagulopathy, the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has transformed APL into a highly curable disease with long-term cure rates exceeding 90% in the current era [ 2 , 3 ]. … Arsenic Trioxide Decreases Lymphangiogenesis by Inducing Apoptotic Pathways and Inhibition of Important Endothelial Cell Receptors Curr. Issues Mol. Biol. 2024 46 67 80 10.3390/cimb46010006 38275666 PMC10813910 …

Arrhythmias, conduction disorders and sudden cardiac death in cancer patients and survivors: expert opinion of the working groups on cardio-oncology and on electrophysiology of the hellenic cardiac society.

Advances in cancer therapeutics have significantly improved patient survival; however, cardiotoxic effects-including arrhythmias-have emerged as a growing clinical concern. This expert opinion, developed by the Working Groups on Cardio-Oncology and Electrophysiology of the Hellenic Cardiological Society, aims to raise awareness of the increasing burden of arrhythmias in cancer patients and survivors. This document explores the multifactorial etiology of arrhythmias in this population, including patient-related factors, the direct effects of malignancy, and the arrhythmogenic potential of thera

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… Arsenic trioxide, a differentiation agent, has demonstrated to induce sinus tachycardia, premature ventricular complexes, QTc prolongation, TdP and more rarely bradycardia and heart blocks [ 19 , 20 ]. … Chemotherapeutic agents can impair cardiac repolarization through direct effects on ionic channels (arsenic trioxide, TKIs) or by inducing myocyte injury [ 18 ]. The list of chemotherapeutics that can lead to QTc prolongation is extensive. …

Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.

The past decade has seen significant advances in our understanding of Hedgehog (HH) signaling pathway in various biological events. HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium. HH signaling pathway has important functions in embryonic development and tissue homeostasis. It plays a central role in the regulation of the proliferation and differentiation of adult stem cells. Importantly, it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence, malignant progression, poor progn

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… BCC basal cell carcinomas, AML acute myeloid leukemia, APL acute promyelocytic leukemia In 2000, the first drug targeting HH signaling pathway, arsenic trioxide (ATO), was approved for the treatment of acute promyelocytic leukemia (APL). 373 ATO not only inhibits HH signaling pathway, but also targets …

High-Dose Vitamin C in Advanced-Stage Cancer Patients.

High-dose intravenously administered vitamin C (IVC) is widely used in cancer patients by complementary and alternative medicine practitioners. The most frequent indications for IVC therapy result from the belief in its effectiveness as a potent anti-cancer agent which additionally enhances chemosensitivity of cancer cells and reduces chemotherapy-related toxicities and fatigue intensity. In this narrative review, we decided to deal with this issue, trying to answer the question whether there is any scientific evidence supporting the rationale for application of high-dose IVC therapy in advanc

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… In addition, in the studies evaluating the safety of IVC administered simultaneously with the standard treatment of drug-resistant multiple myeloma (arsenic trioxide in monotherapy, arsenic trioxide/dexamethasone, and arsenic trioxide/bortezomib), therapy-related toxicities were related mainly to arsenic … trioxide properties [ 109 , 110 , 111 , 112 ]. …

15th Report on Carcinogens.

BACKGROUND: The Report on Carcinogens (RoC) is a congressionally mandated, science-based public health document that the National Toxicology Program (NTP) prepares for the U.S. Department of Health and Human Services Secretary. The latest cumulative report, the 15th RoC, includes 256 listings of substances - chemical, physical, and biological agents; mixtures; and exposure circumstances - that are known or reasonably anticipated to cause cancer in humans. For each listed substance, a profile, i.e., a short synopsis of key studies on cancer, exposure data, and regulations to limit exposure, is

An appraisal of drug development timelines in the Era of precision oncology.

The effects of incorporating a biomarker-based (personalized or precision) selection strategy on drug development timelines for new oncology drugs merit investigation. Here we accessed documents from the Food and Drug Administration (FDA) database for anticancer agents approved between 09/1998 and 07/2014 to compare drugs developed with and without a personalized strategy. Sixty-three drugs were included (28 [44%] personalized and 35 [56%] non-personalized). No differences in access to FDA-expedited programs were observed between personalized and non-personalized drugs. A personalized approach

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… Figure 1 Flow chart of drug selection Table 1 Comparison of personalized versus non-personalized drugs * two drugs were not included because IND submission was not available (decitabine and arsenic trioxide). Abbreviations: IND, investigational new drug. … Arsenic trioxide and decitabine were included only on approval phase analysis due to absence of IND information. Median duration of clinical phase of development was 75.4 months ( N = 61 drugs, 95% CI 67.2–94.8) and median approval time was 6.0 months ( N = 63 drugs, 95% CI 6.0–7.8). …

Acute Promyelocytic Leukemia in a Woman with Thalassemia Intermedia: Case Report and Review of Literature on Hematological Malignancies in β-Thalassemia Patients.

Patients affected by transfusion-dependent β-thalassemia are prone to developing several clinical complications, mostly related to the iron overload. We report the case of a patient affected by transfusion-dependent β-thalassemia (TDT) developing acute promyelocytic leukemia (APL). In our case, the therapeutic management was significantly complicated not only by myocardial dysfunction, but also by the occurrence of the differentiation syndrome following all-trans retinoic acid (ATRA) administration. We carried out a careful revision of the current literature on the occurrence of hematological

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… Accordingly, our patient was deemed unfit to receive arsenic trioxide despite the intermediate risk of APL. One of the most striking features of our patient was the susceptibility to developing pulmonary disease following ATRA exposure. … We therefore recommend caution in the use of cardiotoxic drug (anthracycline, arsenic trioxide), with a baseline cardiac evaluation and a strict monitoring during therapy, especially in patients with a pre-existing thalassemia-related cardiomyopathy. …